Artykuły w czasopismach na temat „MicroRNA”
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Varga, Zoltán V., Ágnes Zvara, Nóra Faragó, Gabriella F. Kocsis, Márton Pipicz, Renáta Gáspár, Péter Bencsik i in. "MicroRNAs associated with ischemia-reperfusion injury and cardioprotection by ischemic pre- and postconditioning: protectomiRs". American Journal of Physiology-Heart and Circulatory Physiology 307, nr 2 (15.07.2014): H216—H227. http://dx.doi.org/10.1152/ajpheart.00812.2013.
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We aimed to characterize early changes in microRNA expression in acute cardioprotection by ischemic pre- and postconditioning in rat hearts. Hearts isolated from male Wistar rats were subjected to 1) time-matched nonischemic perfusion, 2) ischemia-reperfusion (30 min of coronary occlusion and 120 min of reperfusion), 3) preconditioning (3 × 5 min of coronary occlusion) followed by ischemia-reperfusion, or 4) ischemia-reperfusion with postconditioning (6 × 10 s of global ischemia-reperfusion at the onset of reperfusion). Infarct size was significantly reduced by both interventions. Of 350 different microRNAs assessed by microarray analysis, 147–160 microRNAs showed detectable expression levels. Compared with microRNA alterations induced by ischemia-reperfusion versus time-matched nonischemic controls, five microRNAs were significantly affected by both pre- and postconditioning (microRNA-125b*, microRNA-139-3p, microRNA-320, microRNA-532-3p, and microRNA-188), four microRNAs were significantly affected by preconditioning (microRNA-487b, microRNA-139-5p, microRNA-192, and microRNA-212), and nine microRNAs were significantly affected by postconditioning (microRNA-1, microRNA let-7i, microRNA let-7e, microRNA let-7b, microRNA-181a, microRNA-208, microRNA-328, microRNA-335, and microRNA-503). Expression of randomly selected microRNAs was validated by quantitative real-time PCR. By a systematic comparison of the direction of microRNA expression changes in all groups, we identified microRNAs, specific mimics, or antagomiRs that may have pre- and postconditioning-like cardioprotective effects (protectomiRs). Transfection of selected protectomiRs (mimics of microRNA-139-5p, microRNA-125b*, microRNA let-7b, and inhibitor of microRNA-487b) into cardiac myocytes subjected to simulated ischemia-reperfusion showed a significant cytoprotective effect. This is the first demonstration that the ischemia-reperfusion-induced microRNA expression profile is significantly influenced by both pre- and postconditioning, which shows the involvement of microRNAs in cardioprotective signaling. Moreover, by analysis of microRNA expression patterns in cardioprotection by pre- and postconditioning, specific protectomiRs can be revealed as potential therapeutic tools for the treatment of ischemia-reperfusion injury.
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Liu, Zhong, Yong-Hua Tuo, Jian-Wen Chen, Qing-Yuan Wang, Songlin Li, Ming-Chang Li, Gang Dai i in. "NADPH oxidase inhibitor regulates microRNAs with improved outcome after mechanical reperfusion". Journal of NeuroInterventional Surgery 9, nr 7 (20.06.2016): 702–6. http://dx.doi.org/10.1136/neurintsurg-2016-012463.
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BackgroundInhibition of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) pathway improves the neurological outcome in the transient middle cerebral artery occlusion (tMCAO) animal model. In this study we analyzed the microRNAs profile targeting NOX2 and NOX4 genes and its response to NOX2/4 inhibitor VAS2870 to understand the mechanisms of this protective effect.MethodsThe intraluminal filament tMCAO model was established in hyperglycemic rats (n=106) with 5 hours ischemia followed by 19 hours reperfusion. NOX inhibitor VAS2870 was delivered intravenously before reperfusion. Infarct volume, hemorrhagic transformation, and mortality were determined at 24 hours after cerebral ischemia. MicroRNAs profile targeting NOX2 and NOX4 genes were predicted by microRNA databases and further evaluated by microRNA microarray and quantitative RT-PCR.ResultsTen microRNAs potentially targeting NOX2 and NOX4 genes (including microRNA-29a, microRNA-29c, microRNA-126a, microRNA-132, microRNA-136, microRNA-138, microRNA-139, microRNA-153, microRNA-337, and microRNA-376a) were significantly downregulated in the ischemic hemisphere in the tMCAO group compared with the sham-operated group, as shown by microRNA microarray and quantitative RT-PCR (all p<0.05). Intravenous treatment with NOX inhibitor VAS2870 before reperfusion increased the expression of microRNA-29a, microRNA-29c, microRNA-126a, and microRNA-132 compared with the tMCAO group (all p<0.05).ConclusionsSeveral microRNAs potentially targeting NOX2 and NOX4 genes displayed altered levels in hyperglycemic rats with the tMCAO model, suggesting their regulatory roles and targeting potentials for acute ischemic stroke treatment. Targeting specific microRNAs may represent a novel intervention opportunity to improve outcome and reduce hemorrhagic transformation after mechanical reperfusion for acute ischemic stroke.
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Zinovyeva, Anna Y., Isana Veksler-Lublinsky, Ajay A. Vashisht, James A. Wohlschlegel i Victor R. Ambros. "Caenorhabditis elegans ALG-1 antimorphic mutations uncover functions for Argonaute in microRNA guide strand selection and passenger strand disposal". Proceedings of the National Academy of Sciences 112, nr 38 (8.09.2015): E5271—E5280. http://dx.doi.org/10.1073/pnas.1506576112.
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MicroRNAs are regulators of gene expression whose functions are critical for normal development and physiology. We have previously characterized mutations in a Caenorhabditis elegans microRNA-specific Argonaute ALG-1 (Argonaute-like gene) that are antimorphic [alg-1(anti)]. alg-1(anti) mutants have dramatically stronger microRNA-related phenotypes than animals with a complete loss of ALG-1. ALG-1(anti) miRISC (microRNA induced silencing complex) fails to undergo a functional transition from microRNA processing to target repression. To better understand this transition, we characterized the small RNA and protein populations associated with ALG-1(anti) complexes in vivo. We extensively characterized proteins associated with wild-type and mutant ALG-1 and found that the mutant ALG-1(anti) protein fails to interact with numerous miRISC cofactors, including proteins known to be necessary for target repression. In addition, alg-1(anti) mutants dramatically overaccumulated microRNA* (passenger) strands, and immunoprecipitated ALG-1(anti) complexes contained nonstoichiometric yields of mature microRNA and microRNA* strands, with some microRNA* strands present in the ALG-1(anti) Argonaute far in excess of the corresponding mature microRNAs. We show complex and microRNA-specific defects in microRNA strand selection and microRNA* strand disposal. For certain microRNAs (for example mir-58), microRNA guide strand selection by ALG-1(anti) appeared normal, but microRNA* strand release was inefficient. For other microRNAs (such as mir-2), both the microRNA and microRNA* strands were selected as guide by ALG-1(anti), indicating a defect in normal specificity of the strand choice. Our results suggest that wild-type ALG-1 complexes recognize structural features of particular microRNAs in the context of conducting the strand selection and microRNA* ejection steps of miRISC maturation.
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Jongen-Lavrencic, Mojca, Su Ming Sun, Menno K. Dijkstra, Peter J. M. Valk i Bob Löwenberg. "MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia". Blood 111, nr 10 (15.05.2008): 5078–85. http://dx.doi.org/10.1182/blood-2008-01-133355.
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Abstract Acute myeloid leukemia (AML) is a highly diverse disease characterized by various cytogenetic and molecular abnormalities. MicroRNAs are small noncoding RNAs that show variable expression during myeloid differentiation. MicroRNA expression in marrow blasts in 215 cases of newly diagnosed and (cyto)genetically defined AML was assessed using quantitative reverse-transcription–polymerase chain reaction (RT-PCR) for 260 human microRNAs. In the same series, mRNA gene expression profiles were established, allowing a direct comparison between microRNA and mRNA expression. We show that microRNA expression profiling following unsupervised analysis reveals distinctive microRNA signatures that correlate with cytogenetic and molecular subtypes of AML (ie, AMLs with t(8;21), t(15;17), inv(16), NPM1, and CEBPA mutations). Significantly differentially expressed microRNAs for genetic subtypes of AML were identified. Specific microRNAs with established oncogenic and tumor suppressor functions, such as microRNA-155, microRNA-21, and let-7, appear to be associated with particular subtypes. Combinations of selected sets of microRNAs could predict cytogenetically normal AML with mutations in the genes of NPM1 and CEBPA and FLT3-ITD with similar accuracy as mRNA probe set combinations defined by gene expression profiling. MicroRNA expression apparently bears specific relationships to the heterogeneous pathobiology of AML. Distinctive microRNA signatures appear of potential value in the clinical diagnosis of AML.
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Marcucci, Guido, Krzysztof Mrózek, Michael D. Radmacher, Ramiro Garzon i Clara D. Bloomfield. "The prognostic and functional role of microRNAs in acute myeloid leukemia". Blood 117, nr 4 (27.01.2011): 1121–29. http://dx.doi.org/10.1182/blood-2010-09-191312.
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Abstract Expression of microRNAs, a new class of noncoding RNAs that hybridize to target messenger RNA and regulate their translation into proteins, has been recently demonstrated to be altered in acute myeloid leukemia (AML). Distinctive patterns of increased expression and/or silencing of multiple microRNAs (microRNA signatures) have been associated with specific cytogenetic and molecular subsets of AML. Changes in the expression of several microRNAs altered in AML have been shown to have functional relevance in leukemogenesis, with some microRNAs acting as oncogenes and others as tumor suppressors. Both microRNA signatures and a single microRNA (ie, miR-181a) have been shown to supply prognostic information complementing that gained from cytogenetics, gene mutations, and altered gene expression. Moreover, it has been demonstrated experimentally that antileukemic effects can be achieved by modulating microRNA expression by pharmacologic agents and/or increasing low endogenous levels of microRNAs with tumor suppressor function by synthetic microRNA oligonucleotides, or down-regulating high endogenous levels of leukemogenic microRNAs by antisense oligonucleotides (antagomirs). Therefore, it is reasonable to predict the development of novel microRNA-based therapeutic approaches in AML. We review herein results of current studies analyzing changes of microRNA expression in AML and discuss their potential biologic, diagnostic, and prognostic relevance.
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Kiseleva, Y. Y., K. G. Ptitsyn, S. P. Radko, V. G. Zgoda i A. I. Archakov. "Digital droplet PCR - a prospective technological approach to quantitative profiling of microRNA". Biomeditsinskaya Khimiya 62, nr 4 (2016): 403–10. http://dx.doi.org/10.18097/pbmc20166204403.
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MicroRNA is a special type of regulatory molecules governing gene expression. Circulating microRNAs found in blood and other biological fluids are considered today as potential biomarkers of human pathology. Presently, quantitative alterations of particular microRNAs are revealed for a large number of oncological diseases and other disorders. The recently emerged method of digital droplet PCR (ddPCR) possesses a number of advantages making this method the most suitable for verification and validation of perspective microRNA markers of human pathologies. Among these advantages are the high accuracy and reproducibility of microRNA quantification as well as the capability to directly measure the absolute number of microRNA copies with the large dynamic range and a high throughput. The paper reviews microRNA biogenesis, the origin of circulating microRNAs, and methods used for their quantification. The special technical features of ddPCR, which make it an attractive method both for studying microRNAs as biomarkers of human pathologies and for basic research devoted to aspects of gene regulation by microRNA molecules, are also discussed.
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Li, Li-Jie, Wei-Min Chang i Michael Hsiao. "Aberrant Expression of microRNA Clusters in Head and Neck Cancer Development and Progression: Current and Future Translational Impacts". Pharmaceuticals 14, nr 3 (27.02.2021): 194. http://dx.doi.org/10.3390/ph14030194.
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MicroRNAs are small non-coding RNAs known to negative regulate endogenous genes. Some microRNAs have high sequence conservation and localize as clusters in the genome. Their coordination is regulated by simple genetic and epigenetic events mechanism. In cells, single microRNAs can regulate multiple genes and microRNA clusters contain multiple microRNAs. MicroRNAs can be differentially expressed and act as oncogenic or tumor suppressor microRNAs, which are based on the roles of microRNA-regulated genes. It is vital to understand their effects, regulation, and various biological functions under both normal and disease conditions. Head and neck squamous cell carcinomas are some of the leading causes of cancer-related deaths worldwide and are regulated by many factors, including the dysregulation of microRNAs and their clusters. In disease stages, microRNA clusters can potentially control every field of oncogenic function, including growth, proliferation, apoptosis, migration, and intercellular commutation. Furthermore, microRNA clusters are regulated by genetic mutations or translocations, transcription factors, and epigenetic modifications. Additionally, microRNA clusters harbor the potential to act therapeutically against cancer in the future. Here, we review recent advances in microRNA cluster research, especially relative to head and neck cancers, and discuss their regulation and biological functions under pathological conditions as well as translational applications.
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Qin, Li-Xuan. "An Integrative Analysis of microRNA and mRNA Expression–-A Case Study". Cancer Informatics 6 (styczeń 2008): CIN.S633. http://dx.doi.org/10.4137/cin.s633.
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Background MicroRNAs are believed to play an important role in gene expression regulation. They have been shown to be involved in cell cycle regulation and cancer. MicroRNA expression profiling became available owing to recent technology advancement. In some studies, both microRNA expression and mRNA expression are measured, which allows an integrated analysis of microRNA and mRNA expression. Results We demonstrated three aspects of an integrated analysis of microRNA and mRNA expression, through a case study of human cancer data. We showed that (1) microRNA expression efficiently sorts tumors from normal tissues regardless of tumor type, while gene expression does not; (2) many microRNAs are down-regulated in tumors and these microRNAs can be clustered in two ways: microRNAs similarly affected by cancer and microRNAs similarly interacting with genes; (3) taking let-7f as an example, targets genes can be identified and they can be clustered based on their relationship with let-7f expression. Discussion Our findings in this paper were made using novel applications of existing statistical methods: hierarchical clustering was applied with a new distance measure–the co-clustering frequency–to identify sample clusters that are stable; microRNA-gene correlation profiles were subject to hierarchical clustering to identify microRNAs that similarly interact with genes and hence are likely functionally related; the clustering of regression models method was applied to identify microRNAs similarly related to cancer while adjusting for tissue type and genes similarly related to microRNA while adjusting for disease status. These analytic methods are applicable to interrogate multiple types of -omics data in general.
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Karkhane, Maryam, Hamed Esmaeil Lashgarian, Maryam Hormozi, Shirzad Fallahi, Kourosh Cheraghipour i Abdolrazagh Marzban. "Oncogenesis and Tumor Inhibition by MicroRNAs and its Potential Therapeutic Applications: A Systematic Review". MicroRNA 9, nr 3 (13.04.2020): 198–215. http://dx.doi.org/10.2174/2211536608666191104103834.
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MicroRNAs appear as small molecule modifiers, which improve many new findings and mechanical illustrations for critically important biological phenomena and pathologic events. The best-characterized non‐coding RNA family consists of about 2600 human microRNAs. Rich evidence has revealed their crucial importance in maintaining normal development, differentiation, growth control, aging, modulation of cell survival or apoptosis, as well as migration and metastasis as microRNAs dysregulation leads to cancer incidence and progression. By far, microRNAs have recently emerged as attractive targets for therapeutic intervention. The rationale for developing microRNA therapeutics is based on the premise that aberrantly expressed microRNAs play a significant role in the emergence of a variety of human diseases ranging from cardiovascular defects to cancer, and that repairing these microRNA deficiencies by either antagonizing or restoring microRNA function may yield a therapeutic benefit. Although microRNA antagonists are conceptually similar to other inhibitory therapies, improving the performance of microRNAs by microRNA replacement or inhibition that is a less well- described attitude. In this assay, we have condensed the last global knowledge and concepts regarding the involvement of microRNAs in cancer emergence, which has been achieved from the previous studies, consisting of the regulation of key cancer‐related pathways, such as cell cycle control and the DNA damage response and the disruption of profile expression in human cancer. Here, we have reviewed the special characteristics of microRNA replacement and inhibition therapies and discussed explorations linked with the delivery of microRNA mimics in turmeric cells. Besides, the achievement of biomarkers based on microRNAs in clinics is considered as novel non-invasive biomarkers in diagnostic and prognostic assessments.
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Zhang, Xiaomin, Gohar Azhar, Emmanuel D. Williams, Steven C. Rogers i Jeanne Y. Wei. "MicroRNA Clusters in the Adult Mouse Heart: Age-Associated Changes". BioMed Research International 2015 (2015): 1–12. http://dx.doi.org/10.1155/2015/732397.
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The microRNAs and microRNA clusters have been implicated in normal cardiac development and also disease, including cardiac hypertrophy, cardiomyopathy, heart failure, and arrhythmias. Since a microRNA cluster has from two to dozens of microRNAs, the expression of a microRNA cluster could have a substantial impact on its target genes. In the present study, the configuration and distribution of microRNA clusters in the mouse genome were examined at various inter-microRNA distances. Three important microRNA clusters that are significantly impacted during adult cardiac aging, the miR-17-92, miR-106a-363, and miR-106b-25, were also examined in terms of their genomic location, RNA transcript character, sequence homology, and their relationship with the corresponding microRNA families. Multiple microRNAs derived from the three clusters potentially target various protein components of the cdc42-SRF signaling pathway, which regulates cytoskeleton dynamics associated with cardiac structure and function. The data indicate that aging impacted the expression of both guide and passenger strands of the microRNA clusters; nutrient stress also affected the expression of the three microRNA clusters. The miR-17-92, miR-106a-363, and miR-106b-25 clusters are likely to impact the Cdc42-SRF signaling pathway and thereby affect cardiac morphology and function during pathological conditions and the aging process.
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Ohlsson Teague, E. M. C., V. Nisenblat, S. A. Robertson i M. L. Hull. "506. MENSTRUAL CYCLE VARIATIONS IN PLASMA microRNA EXPRESSION PROFILES". Reproduction, Fertility and Development 21, nr 9 (2009): 106. http://dx.doi.org/10.1071/srb09abs506.
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microRNAs are short, single-stranded RNAs that regulate gene expression at the post-transcriptional level. Plasma and serum microRNAs correlate closely with microRNA profiles of diseased tissue and have been explored as blood-based biomarkers for human diseases, including steroid-driven malignancies. However, reproductive steroid signalling regulates the expression of specific microRNAs and this could impact the utility of microRNA biomarkers in reproductive aged women. We hypothesised that microRNA expression profiles are altered by steroid hormone fluctuations associated with the menstrual cycle. To test this hypothesis, plasma microRNA expression was measured in healthy women at 3 stages of a 28 day menstrual cycle; ie menstrual (day 3-5), follicular (day 9–13) and implantation window/secretory phase (day 18–22). Total RNA was extracted from plasma, multiplex reverse transcription was performed, and the cDNA pre-amplified prior to expression analysis of 667 microRNAs on Taqman low density PCR arrays (n=6 women). Preliminary data shows that up to 200 microRNAs may be detected with this methodology, and that at least 14 of these are differentially expressed (fold change ≥±1.5) at follicular and secretory phase, as compared to menstrual phase. We plan to confirm these findings with standard Taqman microRNA assays (n=10 women). Our findings suggest that plasma miRNA expression profiles change over the menstrual cycle, and that this could confound microRNA-based diagnostic tests. We hope to demonstrate the most appropriate cycle phase for blood-based miRNA profiling, facilitating the development of plasma microRNA-based diagnostic tests and providing valuable information to researchers studying circulating microRNA profiles in reproductive aged women.
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Rana, Indrajeetsinh, Elena Velkoska, Sheila K. Patel, Louise M. Burrell i Fadi J. Charchar. "MicroRNAs mediate the cardioprotective effect of angiotensin-converting enzyme inhibition in acute kidney injury". American Journal of Physiology-Renal Physiology 309, nr 11 (1.12.2015): F943—F954. http://dx.doi.org/10.1152/ajprenal.00183.2015.
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Cardiovascular disease, including cardiac hypertrophy, is common in patients with kidney disease and can be partially attenuated using blockers of the renin-angiotensin system (RAS). It is unknown whether cardiac microRNAs contribute to the pathogenesis of cardiac hypertrophy or to the protective effect of RAS blockade in kidney disease. Using a subtotal nephrectomy rat model of kidney injury, we investigated changes in cardiac microRNAs that are known to have direct target genes involved in the regulation of apoptosis, fibrosis, and hypertrophy. The effect of treatment with the angiotensin-converting enzyme (ACE) inhibitor ramipril on cardiac microRNAs was also investigated. Kidney injury led to a significant increase in cardiac microRNA-212 and microRNA-132 expression. Ramipril reduced cardiac hypertrophy, attenuated the increase in microRNA-212 and microRNA-132, and significantly increased microRNA-133 and microRNA-1 expression. There was altered expression of caspase-9, B cell lymphoma-2, transforming growth factor-β, fibronectin 1, collagen type 1A1, and forkhead box protein O3, which are all known to be involved in the regulation of apoptosis, fibrosis, and hypertrophy in cardiac cells while being targets for the above microRNAs. ACE inhibitor treatment increased expression of microRNA-133 and microRNA-1. The inhibitory action of ACE inhibitor treatment on increased cardiac NADPH oxidase isoform 1 expression after subtotal nephrectomy surgery suggests that inhibition of oxidative stress is also one of mechanism of ACE inhibitor-mediated cardioprotection. These finding suggests the involvement of microRNAs in the cardioprotective action of ACE inhibition in acute renal injury, which is mediated through an inhibitory action on profibrotic and proapoptotic target genes and stimulatory action on antihypertrophic and antiapoptotic target genes.
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Marta, Gustavo Nader, Bernardo Garicochea, André Lopes Carvalho, Juliana M. Real i Luiz Paulo Kowalski. "MicroRNAs, cancer and ionizing radiation: Where are we?" Revista da Associação Médica Brasileira 61, nr 3 (czerwiec 2015): 275–81. http://dx.doi.org/10.1590/1806-9282.61.03.275.
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Summary The aim of this study is to describe the biogenesis of microRNA, its relations with carcinogenesis, and the correlation between microRNA and ionizing radiation (IR), focusing on radioresponsiveness. It is known that microRNA biogenesis is well established and involves different enzymatic cleavages, resulting in the production of mature microRNA. MicroRNAs are involved in carcinogenesis. Their interaction is related to the genetic and epigenetic changes associated with activation of proto-oncogenes or inactivation of tumor suppressor genes. Several studies have shown that the levels of expression of some microRNAs vary significantly after irradiation. There are evidences that microRNAs can influence cellular response after IR. In addition, microRNAs are related to modulation of the expression of several post-transcriptional targets in DNA damage response pathways, and to the DNA damage repair regulation mechanism. Future studies can clarify a possible clinical use of microRNAs as a new class of radiosensitive agents.
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Trinidad-Barnech, Juan Manuel, Rafael Sebastián Fort, Guillermo Trinidad Barnech, Beatriz Garat i María Ana Duhagon. "Transcriptome-Wide Analysis of microRNA–mRNA Correlations in Tissue Identifies microRNA Targeting Determinants". Non-Coding RNA 9, nr 1 (13.02.2023): 15. http://dx.doi.org/10.3390/ncrna9010015.
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MicroRNAs are small RNAs that regulate gene expression through complementary base pairing with their target mRNAs. A substantial understanding of microRNA target recognition and repression mechanisms has been reached using diverse empirical and bioinformatic approaches, primarily in vitro biochemical or cell culture perturbation settings. We sought to determine if rules of microRNA target efficacy could be inferred from extensive gene expression data of human tissues. A transcriptome-wide assessment of all the microRNA–mRNA canonical interactions’ efficacy was performed using a normalized Spearman correlation (Z-score) between the abundance of the transcripts in the PRAD-TCGA dataset tissues (RNA-seq mRNAs and small RNA-seq for microRNAs, 546 samples). Using the Z-score of correlation as a surrogate marker of microRNA target efficacy, we confirmed hallmarks of microRNAs, such as repression of their targets, the hierarchy of preference for gene regions (3′UTR > CDS > 5′UTR), and seed length (6 mer < 7 mer < 8 mer), as well as the contribution of the 3′-supplementary pairing at nucleotides 13–16 of the microRNA. Interactions mediated by 6 mer + supplementary showed similar inferred repression as 7 mer sites, suggesting that the 6 mer + supplementary sites may be relevant in vivo. However, aggregated 7 mer-A1 seeds appear more repressive than 7 mer-m8 seeds, while similar when pairing possibilities at the 3′-supplementary sites. We then examined the 3′-supplementary pairing using 39 microRNAs with Z-score-inferred repressive 3′-supplementary interactions. The approach was sensitive to the offset of the bridge between seed and 3′-supplementary pairing sites, and the pattern of offset-associated repression found supports previous findings. The 39 microRNAs with effective repressive 3′supplementary sites show low GC content at positions 13–16. Our study suggests that the transcriptome-wide analysis of microRNA–mRNA correlations may uncover hints of microRNA targeting determinants. Finally, we provide a bioinformatic tool to identify microRNA–mRNA candidate interactions based on the sequence complementarity of the seed and 3′-supplementary regions.
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Thapa, JB. "MicroRNA in modern genetics". Journal of Pathology of Nepal 2, nr 4 (25.09.2012): 313–16. http://dx.doi.org/10.3126/jpn.v2i4.6886.
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In recent years microRNAs have emerged as important players in modern genetics. This review attempts to introduce the biogenesis of microRNA and its important physiological role in protein synthesis. The association of microRNA with different cancers is discussed. Lastly the frontier field of therapy based on microRNAs to treat different diseases is introduced.Journal of Pathology of Nepal (2012) Vol. 2, 313-316DOI: http://dx.doi.org/10.3126/jpn.v2i4.6886
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Thomassen, Gard O. S., Øystein Røsok i Torbjørn Rognes. "Computational Prediction of MicroRNAs Encoded in Viral and Other Genomes". Journal of Biomedicine and Biotechnology 2006 (2006): 1–10. http://dx.doi.org/10.1155/jbb/2006/95270.
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We present an overview of selected computational methods for microRNA prediction. It is especially aimed at viral miRNA detection. As the number of microRNAs increases and the range of genomes encoding miRNAs expands, it seems that these small regulators have a more important role than has been previously thought. Most microRNAs have been detected by cloning and Northern blotting, but experimental methods are biased towards abundant microRNAs as well as being time-consuming. Computational detection methods must therefore be refined to serve as a faster, better, and more affordable method for microRNA detection. We also present data from a small study investigating the problems of computational miRNA prediction. Our findings suggest that the prediction of microRNA precursor candidates is fairly easy, while excluding false positives as well as exact prediction of the mature microRNA is hard. Finally, we discuss possible improvements to computational microRNA detection.
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Hydbring, Per, i Gayane Badalian-Very. "Clinical applications of microRNAs". F1000Research 2 (6.06.2013): 136. http://dx.doi.org/10.12688/f1000research.2-136.v1.
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MicroRNAs represent a class of small RNAs derived from polymerase II controlled transcriptional regions. The primary transcript forms one or several bulging double stranded hairpins which are processed by Drosha and Dicer into hetero-duplexes. The targeting microRNA strand of the duplex is incorporated into the RNA Induced Silencing Complex from where it silences up to hundreds of mRNA transcript by inducing mRNA degradation or blocking protein translation. Apart from involvement in a variety of biological processes, microRNAs were early recognized for their potential in disease diagnostics and therapeutics. Due to their stability, microRNAs could be used as biomarkers. Currently, there are microRNA panels helping physicians determining the origins of cancer in disseminated tumors. The development of microRNA therapeutics has proved more challenging mainly due to delivery issues. However, one drug is already in clinical trials and several more await entering clinical phases. This review summarizes what has been recognized pre-clinically and clinically on diagnostic microRNAs. In addition, it highlights individual microRNA drugs in running platforms driven by four leading microRNA-therapeutic companies.
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Bi, Kefan, Xujun Zhang, Wenbiao Chen i Hongyan Diao. "MicroRNAs Regulate Intestinal Immunity and Gut Microbiota for Gastrointestinal Health: A Comprehensive Review". Genes 11, nr 9 (12.09.2020): 1075. http://dx.doi.org/10.3390/genes11091075.
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MicroRNAs are small non-coding RNAs regulating gene expression at the post-transcriptional level. The regulation of microRNA expression in the gut intestine is gradually recognized as one of the crucial contributors of intestinal homeostasis and overall health. Recent studies indicated that both the microRNAs endogenous in the gut intestine and exogenous from diets could play influential roles in modulating microbial colonization and intestinal immunity. In this review, we discuss the biological functions of microRNAs in regulating intestinal homeostasis by modulating intestinal immune responses and gut microbiota. We particularly focus on addressing the microRNA-dependent communication and interactions among microRNA, gut microbiota, and intestinal immune system. Besides, we also summarize the roles of diet-derived microRNAs in host-microbiome homeostasis and their benefits on intestinal health. A better understanding of the relationships among intestinal disorders, microRNAs, and other factors influencing intestinal health can facilitate the application of microRNA-based therapeutics for gastrointestinal diseases.
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Lieberman, Judy. "Micromanipulating Hematological Malignancies and Other Cancers". Blood 116, nr 21 (19.11.2010): SCI—33—SCI—33. http://dx.doi.org/10.1182/blood.v116.21.sci-33.sci-33.
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Abstract Abstract SCI-33 MicroRNAs regulate the response of the cell to environmental changes and developmental cues. microRNA expression is dysregulated in cancer – microRNA expression is generally reduced in cancer cells compared to normal tissue and individual microRNAs, termed oncomirs, that act as tumor suppressor genes or oncogenes are frequently aberrantly expressed in cancer and their expression can be linked to prognosis and response to therapy. Because microRNAs regulate cancer cell differentiation, proliferation, survival, and metastasis, manipulating microRNA function, either by mimicking or inhibiting miRNAs implicated in cancer, could provide a powerful therapeutic strategy to interfere with key pathways for cancer progression. This talk will explore some of the opportunities and obstacles to harnessing microRNA biology for cancer therapy. Disclosures: No relevant conflicts of interest to declare.
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Chandrasekaran, Arun Richard, Molly MacIsaac, Paromita Dey, Oksana Levchenko, Lifeng Zhou, Madeline Andres, Bijan K. Dey i Ken Halvorsen. "Cellular microRNA detection with miRacles: microRNA- activated conditional looping of engineered switches". Science Advances 5, nr 3 (marzec 2019): eaau9443. http://dx.doi.org/10.1126/sciadv.aau9443.
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MicroRNAs are short noncoding regulatory RNAs that are increasingly used as disease biomarkers. Detection of microRNAs can be arduous and expensive and often requires amplification, labeling, or radioactive probes. Here, we report a single-step, nonenzymatic microRNA detection assay using conformationally responsive DNA nanoswitches. Termed miRacles (microRNA-activated conditional looping of engineered switches), our assay has subattomole sensitivity and single-nucleotide specificity using an agarose gel electrophoresis readout. We detect cellular microRNAs from nanogram-scale RNA extracts of differentiating muscle cells and multiplex our detection for several microRNAs from one biological sample. We demonstrate 1-hour detection without expensive equipment or reagents, making this assay a compelling alternative to quantitative polymerase chain reaction and Northern blotting.
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Zou, Quan, Jinjin Li, Qingqi Hong, Ziyu Lin, Yun Wu, Hua Shi i Ying Ju. "Prediction of MicroRNA-Disease Associations Based on Social Network Analysis Methods". BioMed Research International 2015 (2015): 1–9. http://dx.doi.org/10.1155/2015/810514.
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MicroRNAs constitute an important class of noncoding, single-stranded, ~22 nucleotide long RNA molecules encoded by endogenous genes. They play an important role in regulating gene transcription and the regulation of normal development. MicroRNAs can be associated with disease; however, only a few microRNA-disease associations have been confirmed by traditional experimental approaches. We introduce two methods to predict microRNA-disease association. The first method, KATZ, focuses on integrating the social network analysis method with machine learning and is based on networks derived from known microRNA-disease associations, disease-disease associations, and microRNA-microRNA associations. The other method, CATAPULT, is a supervised machine learning method. We applied the two methods to 242 known microRNA-disease associations and evaluated their performance using leave-one-out cross-validation and 3-fold cross-validation. Experiments proved that our methods outperformed the state-of-the-art methods.
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Kenny, Aidan, Hazel McArdle, Miguel Calero, Alberto Rabano, Stephen F. Madden, Kellie Adamson, Robert Forster i in. "Elevated Plasma microRNA-206 Levels Predict Cognitive Decline and Progression to Dementia from Mild Cognitive Impairment". Biomolecules 9, nr 11 (13.11.2019): 734. http://dx.doi.org/10.3390/biom9110734.
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The need for practical biomarkers for early diagnosis of Alzheimer’s disease (AD) remains largely unmet. Here we investigated the use of blood-based microRNAs as prognostic biomarkers for AD and their application in a novel electrochemical microfluidic device for microRNA detection. MicroRNA transcriptome was profiled in plasma from patients with mild cognitive impairment (MCI) and AD. MicroRNAs Let-7b and microRNA-206 were validated at elevated levels in MCI and AD, respectively. MicroRNA-206 displayed a strong correlation with cognitive decline and memory deficits. Longitudinal follow-ups over five years identified microRNA-206 increases preceding the onset of dementia. MicroRNA-206 was increased in unprocessed plasma of AD and MCI subjects, detected by our microfluidic device. While increased Let-7b levels in plasma may be used to identify patients with MCI, changes in plasma levels of microRNA-206 may be used to predict cognitive decline and progression towards dementia at an MCI stage. MicroRNA quantification via a microfluidic device could provide a practical cost-effective tool for the stratification of patients with MCI according to risk of developing AD.
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Mironova, O. Iu, M. V. Berdysheva i E. M. Elfimova. "Elfimova. MicroRNA: a clinician’s view of the state of the problem. Part 1. History of the issue". Eurasian heart journal, nr 1 (2.03.2023): 100–107. http://dx.doi.org/10.38109/2225-1685-2023-1-100-107.
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A large amount of genetic information is localized in microRNAs which are a class of non-coding RNAs formed from longer RNA precursors, usually having a length of 19-24 nucleotides and a specific hairpin structure. Although microRNA studies have been started relatively recently, there is no doubt that they play an important role in regulating gene expression at the post-transcriptional level in embryonic development, and are also involved in maintaining the normal functions of adult cells. For the first time, microRNA was discovered in the study of free-living nematodes Caenorhabditis elegans and then a new mechanism for suppressing expression using antisense RNA was discovered. MicroRNA may be part of protein-coding transcripts or may be located in the intergenic genome regions. Changes in the functional activity and number of microRNAs can lead to diseases such as oncological, cardiovascular, gynecological, and neurological. MicroRNA is also involved in the process of neurodegeneration and the development of mental diseases. Since part of the microRNA is specific to certain tissues and/or stages of development of the organism, microRNA molecules can be considered as a promising diagnostic tool. Among the advantages of these biomarkers are the possibility of detecting pathology in the latent stage, the low invasiveness of studies and resistance to destructive factors. At the same time, microRNAs can be detected in various biological fluids: blood serum, urine, seminal fluid, saliva, breast milk. Currently, the possibilities of using microRNAs in targeted therapy are widely discussed in connection with the possibility of regulating the expression of genes with undesirable properties or overexpression of microRNA inhibitors to prevent the negative effects of microRNAs that cause the development of the disease. The first part of the review discusses the historical aspect of the study of microRNAs, their mechanism of formation, the features of circulating microRNAs and the possible therapeutic effect of exogenous microRNAs coming from food on the human body.
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Wagenseller, Aubrey G., Amber L. Shada, Kevin D'Auria, Cheryl F. Murphy, Dandan Sun, Kerrington R. Molhoek, Jason A. Papin, Anindya Dutta i Craig L. Slingluff. "MicroRNAs induced in melanoma treated with combination targeted therapy of temsirolimus and bevacizumab." Journal of Clinical Oncology 30, nr 15_suppl (20.05.2012): 8597. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.8597.
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8597 Background: Targeted therapies directed at commonly overexpressed pathways in melanoma have clinical activity in numerous trials. Little is known about how these therapies influence microRNA expression, particularly with combination regimens. A better understanding of how microRNAs are altered with treatment may contribute to understanding mechanisms of therapeutic effects as well as mechanisms of tumor escape from therapy. Methods: Using microRNA arrays, we analyzed microRNA expression levels in melanoma samples from a Cancer Therapy Evaluation Program-sponsored phase II trial of combination temsirolimus and bevacizumab in stage III or IV melanoma, which elicited clinical benefit in a subset of patients. Seventeen patients were treated with temsirolimus for one week, then combination of both temsirolimus and bevacizumab. Metastatic melanoma biopsies were evaluated days 1, 2, and 23. Tumor samples were evaluated from 12 patients. Results: microRNA expression remained unchanged with temsirolimus alone; however, expression of 15 microRNAs was significantly upregulated (1.4 to 2.5-fold) with combination treatment, compared to pre-treatment levels. Interestingly, twelve of these fifteen microRNAs have been reported to possess tumor suppressor capabilities in various cancer types, including melanoma. We identified 15 putative oncogenes and B7-H3, IGF-1, and IGF-1R as potential targets of the 12 tumor suppressor microRNAs, based on published experimental evidence. For 18 of 25 pairings of microRNA and target-mRNA, changes in gene expression from pretreatment to post-combination treatment samples were inversely correlated with changes in microRNA expression, suggesting a functional effect of the microRNA changes induced by combination therapy. Clustering analysis based on selected microRNAs revealed signatures characteristic of clinical response to combination treatment and of tumor BRAF mutational status. Conclusions: We have identified microRNAs that may be involved in the mechanism of action of combination temsirolimus and bevacizumab in metastatic melanoma, possibly through inhibition of oncogenic pathways.
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Funikov, S. Yu, S. S. Ryazansky, A. A. Kanapin, M. D. Logacheva, A. A. Penin, A. V. Snezhkina, V. Yu Shilova, D. G. Garbuz, M. B. Evgen'ev i O. G. Zatsepina. "Interplay between RNA interference and heat shock response systems in Drosophila melanogaster". Open Biology 6, nr 10 (październik 2016): 160224. http://dx.doi.org/10.1098/rsob.160224.
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The genome expression pattern is strongly modified during the heat shock response (HSR) to form an adaptive state. This may be partly achieved by modulating microRNA levels that control the expression of a great number of genes that are embedded within the gene circuitry. Here, we investigated the cross-talk between two highly conserved and universal house-keeping systems, the HSR and microRNA machinery, in Drosophila melanogaster . We demonstrated that pronounced interstrain differences in the microRNA levels are alleviated after heat shock (HS) to form a uniform microRNA pattern. However, individual strains exhibit different patterns of microRNA expression during the course of recovery. Importantly, HS-regulated microRNAs may target functionally similar HS-responsive genes involved in the HSR. Despite the observed general downregulation of primary microRNA precursor expression as well as core microRNA pathway genes after HS, the levels of many mature microRNAs are upregulated. This indicates that the regulation of miRNA expression after HS occurs at transcriptional and post-transcriptional levels. It was also shown that deletion of all hsp70 genes had no significant effect on microRNA biogenesis but might influence the dynamics of microRNA expression during the HSR.
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Pasca, Sergiu, Calin Ionescu, David Andras, Dan Eniu, Mihai Andrei Muresan, Lorand Magdo, Ancuta Jurj i in. "Circulating microRNA-194 and microRNA-1228 Could Predict Colon Cancer Proliferation via Phospho S6 Modulation". Journal of Gastrointestinal and Liver Diseases 29, nr 3 (9.09.2020): 361–67. http://dx.doi.org/10.15403/jgld-2558.
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Background and Aims: Although colon cancer has a decreasing incidence trend in Europe, because of its still high frequency and not fully understood pathogenesis, this malignancy still remains a subject of intense research. The aim of this study was to investigate the role of microRNA-194 and microRNA-1228 in colon cancer proliferation.
Methods: RNA was extracted from patients with colon cancer with or without advanced disease and microRNA expression levels were determined through qRT-PCR. Assays were performed on HCT116 cell line and included qRT-PCR, western blotting and cell counting.
Results: We observed that both microRNAs 194 and 1228 were altered in patients with colon cancer compared with healthy individuals. We observed a lower expression of both microRNA-194 and microRNA-1228 in patients with advanced colon cancer. To validate their pathogenetic role we performed viability and invasion assays on HCT116 cell line transfected with mimics or inhibitors of the mentioned microRNAs, with observable changes in viability and invasion. Furthermore, to determine the altered signaling induced by these microRNAs, we performed western blotting for phospho S6 on HCT116 cells transfected with mimic and inhibitor of the above-mentioned microRNAs with observable differences.
Conclusion: In the current study we have shown that both microRNA-194 and microRNA-1228 alteration was correlated with the presence of advanced colon cancer, a fact that was further validated in vitro through an invasion assay. Moreover, we have also shown that their effect might be mediated through phospho S6 expression.
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Kulkarni, Varun, Juhi Raju Uttamani, Afsar Raza Naqvi i Salvador Nares. "microRNAs: Emerging players in oral cancers and inflammatory disorders". Tumor Biology 39, nr 5 (maj 2017): 101042831769837. http://dx.doi.org/10.1177/1010428317698379.
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Association of oral diseases and disorders with altered microRNA profiles is firmly recognized. These evidences support the potential use of microRNAs as therapeutic tools for diagnosis, prognosis, and treatment of various diseases. In this review, we highlight the association of altered microRNA signatures in oral cancers and oral inflammatory diseases. Advances in our ability to detect microRNAs in human sera and saliva further highlight their clinical value as potential biomarkers. We have discussed key mechanisms underlying microRNA dysregulation in pathological conditions. The use of microRNAs in diagnostics and their potential therapeutic value in the treatment of oral diseases are reviewed.
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DeRaedt, Sarah, Anandi Bierman, Peter van Heusden, Cameron Richards i Alan Christoffels. "microRNA profile of Hermetia illucens (black soldier fly) and its implications on mass rearing". PLOS ONE 17, nr 3 (17.03.2022): e0265492. http://dx.doi.org/10.1371/journal.pone.0265492.
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The growing demands on protein producers and the dwindling available resources have made Hermetia illucens (the black soldier fly, BSF) an economically important species. Insights into the genome of this insect will better allow for robust breeding protocols, and more efficient production to be used as a replacement of animal feed protein. The use of microRNA as a method to understand how gene regulation allows insect species to adapt to changes in their environment, has been established in multiple species. The baseline and life stage expression levels established in this study, allow for insight into the development and sex-linked microRNA regulation in BSF. To accomplish this, microRNA was extracted and sequenced from 15 different libraries with each life stage in triplicate. Of the total 192 microRNAs found, 168 were orthologous to known arthropod microRNAs and 24 microRNAs were unique to BSF. Twenty-six of the 168 microRNAs conserved across arthropods had a statistically significant (p < 0.05) differential expression between Egg to Larval stages. The development from larva to pupa was characterized by 16 statistically significant differentially expressed microRNA. Seven and 9 microRNA were detected as statistically significant between pupa to adult female and pupa to adult male, respectively. All life stages had a nearly equal split between up and down regulated microRNAs. Ten of the unique 24 miRNA were detected exclusively in one life stage. The egg life stage expressed five microRNA (hil-miR-m, hil-miR-p, hil-miR-r, hil-miR-s, and hil-miR-u) not seen in any other life stages. The female adult and pupa life stages expressed one miRNA each hil-miR-h and hil-miR-ac respectively. Both male and female adult life stages expressed hil-miR-a, hil-miR-b, and hil-miR-y. There were no unique microRNAs found only in the larva stage. Twenty-two microRNAs with 56 experimentally validated target genes in the closely related Drosophila melanogaster were identified. Thus, the microRNA found display the unique evolution of BSF, along with the life stages and potential genes to target for robust mass rearing. Understanding of the microRNA expression in BSF will further their use in the crucial search for alternative and sustainable protein sources.
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Jamali, Ali Akbar, Anthony Kusalik i Fang-Xiang Wu. "MDIPA: a microRNA–drug interaction prediction approach based on non-negative matrix factorization". Bioinformatics 36, nr 20 (17.06.2020): 5061–67. http://dx.doi.org/10.1093/bioinformatics/btaa577.
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Abstract Motivation Evidence has shown that microRNAs, one type of small biomolecule, regulate the expression level of genes and play an important role in the development or treatment of diseases. Drugs, as important chemical compounds, can interact with microRNAs and change their functions. The experimental identification of microRNA–drug interactions is time-consuming and expensive. Therefore, it is appealing to develop effective computational approaches for predicting microRNA–drug interactions. Results In this study, a matrix factorization-based method, called the microRNA–drug interaction prediction approach (MDIPA), is proposed for predicting unknown interactions among microRNAs and drugs. Specifically, MDIPA utilizes experimentally validated interactions between drugs and microRNAs, drug similarity and microRNA similarity to predict undiscovered interactions. A path-based microRNA similarity matrix is constructed, while the structural information of drugs is used to establish a drug similarity matrix. To evaluate its performance, our MDIPA is compared with four state-of-the-art prediction methods with an independent dataset and cross-validation. The results of both evaluation methods confirm the superior performance of MDIPA over other methods. Finally, the results of molecular docking in a case study with breast cancer confirm the efficacy of our approach. In conclusion, MDIPA can be effective in predicting potential microRNA–drug interactions. Availability and implementation All code and data are freely available from https://github.com/AliJam82/MDIPA. Supplementary information Supplementary data are available at Bioinformatics online.
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Воропаева, О. Ф., i O. F. Voropaeva. "Deregulation of p53-dependent microRNAs: the results of mathematical modeling". Mathematical Biology and Bioinformatics 12, nr 1 (13.04.2017): 151–75. http://dx.doi.org/10.17537/2017.12.151.
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The mathematical model of the dynamics of the tumor markers network p53–Mdm2–microRNA for microRNA class with a direct positive connection with p53 was formulated. Numerical investigation of the microRNA functioning in conditions of the deregulation of p53 and p53–Mdm2-network was carried out. The deregulation of microRNA in detail was studied. The situations in which p53, its inhibitor Mdm2 and microRNAs exhibit critical properties for the patient's status and can be identified as diagnostic markers of cancer and neurodegenerative disease were studied. The results of numerical analysis are in good agreement with the data of clinical and laboratory studies of known microRNAs.
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Latronico, Michael V. G., Daniele Catalucci i Gianluigi Condorelli. "MicroRNA and cardiac pathologies". Physiological Genomics 34, nr 3 (sierpień 2008): 239–42. http://dx.doi.org/10.1152/physiolgenomics.90254.2008.
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MicroRNA has been shown to be essential for correct cardiovascular development and physiology in a number of recent reports. Studies have also started to characterize the link between specific microRNAs and aspects of pathogenesis—such as chamber morphogenesis, conduction, and contraction—and between microRNA expression signatures and pathological cardiac phenotypes—such as hypertrophy, ischemic cardiomyopathy, dilated cardiomyopathy, and aortic stenosis. Congenital anomalies of the heart may also be associated with the dysregulation of specific microRNAs. Here we report on the latest findings.
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Jardin, Fabrice, Philippe Ruminy, Jean-Pierre Kerckaert, Martin Figeac, Philippe Bertrand, Francoise Parmentier, Jean-Michel Picquenot, Gerard Buchonnet, Christian Bastard i Herve Tilly. "Genomic Regions Supporting microRNA Expression and Their Biogenesis Are Globally Conserved in Diffuse Large B-Cell Lymphomas (DLBCL) and Display a Limited Number of Homozygous Deletions or Amplifications." Blood 110, nr 11 (16.11.2007): 993. http://dx.doi.org/10.1182/blood.v110.11.993.993.
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Abstract MicroRNAs are proposed to play a direct role in oncogenesis as they act as both oncogenes and/or tumour suppressor genes (TSG). MicroRNA deregulation can be explained in some instances by deletion, amplification, translocation or epigenetic mechanisms. However the cause of aberrant expression of specific microRNAs in cancer remains largely unknown. Chromosomal-comparative genomic hybridization (CGH) and higher resolution array-CGH experiments have shown that genomic gains and losses play a crucial role in the development of DLBCL. Whether these gene copy number aberrations may involve specifically microRNA coding regions and be therefore implicated in the dysfunctional expression of microRNAs is currently undetermined. To address this issue, we analyzed 65 de novo DLBCL by array-CGH, using a high resolution microarray that contains ∼ 43,000 probes, giving an average spatial resolution of 35 kB. For each of the 474 microRNAs identified in the human genome (microRNA.sanger, April 2007 registry), 286 probes located near microRNA coding genes or microRNA clusters were defined and used to detect DNA copy alterations involving microRNA coding genes. 21% of the microRNA associated probes displayed a deletion in more than 5% of cases, a rate lower than the rate observed for the entire genome (30%, p =.0008). By contrast, 58% of the microRNA coding regions displayed a DNA copy gain, similarly to the whole genome (61%). Notably, none of the genes coding for components of the biosynthetic pathway (including DGCR8, DICER1-2, Argonaute 1, EIF2C2-3-4, Exportin 5 and DROSHA) displayed recurrent deletions. These results indicate that genomic regions supporting microRNA expression and their biogenesis are globally conserved in DLBCL. However, homozygous microRNA deletions, occurring in more than 5% of cases were observed for some microRNA, namely mir-548a (6%), mir-588 (6%), mir-548b (6%), mir-587 (5%) (all located in the 6q21–23 region), and mir-31 (9p21, 5%), suggesting that these microRNA may act as TSG and/or are located in TSG containing regions. Mir-31 was constantly co-deleted with CDKN2A, a well-defined TSG located in the vicinity. The most frequent amplifications involved mir-92b (1q22, 9%), mir-210 (11p15, 6%), mir-196a-2 (12q13, 6%), mir-148b (12q13, 6%), mir-122a (18q21, 9%), mir-153-1 (2q35, 8%), mir-567 (3q13, 8%), mir-106b (7q22, 9%) and mir-126 (9q34, 8%). Similarly, these genes represent candidate oncogenes or are located in oncogene containing regions. For instance, mir122a was co-amplified with MALT1, located in a close vicinity in 6/6 cases. In addition, distinct patterns of microRNA coding gene copy abnormalities between GCB and ABC subtypes were identified. To conclude, we provide experimental genome wide documentation of DNA copy alterations involving microRNA coding genes in DLBCL and suggest that some still uncharacterized microRNAs may act as TSG or oncogenes. Concordance between microRNA gene copy changes and microRNA gene transcriptional expression is currently investigated.
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Perge, Pál, Zoltán Nagy, Ivan Igaz i Peter Igaz. "Suggested roles for microRNA in tumors". Biomolecular Concepts 6, nr 2 (1.04.2015): 149–55. http://dx.doi.org/10.1515/bmc-2015-0002.
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AbstractMicroRNAs are short non-coding RNA molecules encoded by distinct genes involved in the posttranscriptional regulation of gene expression. Forming part of the epigenetic machinery, microRNAs are involved in several aspects of tumorigenesis. Deregulation of microRNA expression is a common feature of tumors. Overexpressed oncogenic and underexpressed tumor suppressor microRNAs have been described in many different tumors. MicroRNAs are released from tumors that might affect other cells within and outside the tumor. Circulating microRNAs might also be involved in a tumor surveillance mechanism. In this short overview, some important aspects of microRNA in tumors are discussed.
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Muñoz-Alarcón, Andrés, Peter Guterstam, Cristian Romero, Mark A. Behlke, Kim A. Lennox, Jesper Wengel, Samir EL Andaloussi i Ülo Langel. "Modulating Anti-MicroRNA-21 Activity and Specificity Using Oligonucleotide Derivatives and Length Optimization". ISRN Pharmaceutics 2012 (7.02.2012): 1–7. http://dx.doi.org/10.5402/2012/407154.
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MicroRNAs are short, endogenous RNAs that direct posttranscriptional regulation of gene expression vital for many developmental and cellular functions. Implicated in the pathogenesis of several human diseases, this group of RNAs provides interesting targets for therapeutic intervention. Anti-microRNA oligonucleotides constitute a class of synthetic antisense oligonucleotides used to interfere with microRNAs. In this study, we investigate the effects of chemical modifications and truncations on activity and specificity of anti-microRNA oligonucleotides targeting microRNA-21. We observed an increased activity but reduced specificity when incorporating locked nucleic acid monomers, whereas the opposite was observed when introducing unlocked nucleic acid monomers. Our data suggest that phosphorothioate anti-microRNA oligonucleotides yield a greater activity than their phosphodiester counterparts and that a moderate truncation of the anti-microRNA oligonucleotide improves specificity without significantly losing activity. These results provide useful insights for design of anti-microRNA oligonucleotides to achieve both high activity as well as efficient mismatch discrimination.
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Dahiya, Neetu, i Patrice J. Morin. "MicroRNAs in ovarian carcinomas". Endocrine-Related Cancer 17, nr 1 (marzec 2010): F77—F89. http://dx.doi.org/10.1677/erc-09-0203.
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The molecular mechanisms involved in epithelial ovarian cancer initiation and progression are just beginning to be elucidated. In particular, it has become evident that microRNAs (miRNAs or miRs), a class of molecules that post-transcriptionally regulate gene expression, play a major role in ovarian tumorigenesis. Several microRNA profiling studies have identified changes in microRNA patterns that take place during ovarian cancer development. While most deregulated microRNAs are down-regulated in cancer, and may therefore act as tumor suppressors, others are elevated and may represent novel oncogenes in this disease. A number of microRNAs identified as aberrantly expressed in ovarian carcinoma have been shown to have important functional roles in cancer development and may therefore represent targets for therapy. In addition, some of the microRNA patterns may have prognostic significance. The identification of functional targets represents a major hurdle in our understanding of microRNA function in ovarian carcinoma, but significant progress is being made. It is hoped that a better understanding of the microRNA expression and roles in ovarian cancer may provide new avenues for the detection, diagnosis, and therapy of this deadly disease.
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Smith, Bethany, Priyanka Agarwal i Neil A. Bhowmick. "MicroRNA applications for prostate, ovarian and breast cancer in the era of precision medicine". Endocrine-Related Cancer 24, nr 5 (maj 2017): R157—R172. http://dx.doi.org/10.1530/erc-16-0525.
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The high degree of conservation in microRNA fromCaenorhabditiselegansto humans has enabled relatively rapid implementation of findings in model systems to the clinic. The convergence of the capacity for genomic screening being implemented in the prevailing precision medicine initiative and the capabilities of microRNA to address these changes holds significant promise. However, prostate, ovarian and breast cancers are heterogeneous and face issues of evolving therapeutic resistance. The transforming growth factor-beta (TGFβ) signaling axis plays an important role in the progression of these cancers by regulating microRNAs. Reciprocally, microRNAs regulateTGFβactions during cancer progression. One must consider the expression of miRNA in the tumor microenvironment a source of biomarkers of disease progression and a viable target for therapeutic targeting. The differential expression pattern of microRNAs in health and disease, therapeutic response and resistance has resulted in its application as robust biomarkers. With two microRNA mimetics in ongoing restorative clinical trials, the paradigm for future clinical studies rests on the current observational trials to validate microRNA markers of disease progression. Some of today’s biomarkers can be translated to the next generation of microRNA-based therapies.
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Ikeda, Sadakatsu, Sek Won Kong, Jun Lu, Egbert Bisping, Hao Zhang, Paul D. Allen, Todd R. Golub, Burkert Pieske i William T. Pu. "Altered microRNA expression in human heart disease". Physiological Genomics 31, nr 3 (listopad 2007): 367–73. http://dx.doi.org/10.1152/physiolgenomics.00144.2007.
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MicroRNAs are recently discovered regulators of gene expression and are becoming increasingly recognized as important regulators of heart function. Genome-wide profiling of microRNAs in human heart failure has not been reported previously. We measured expression of 428 microRNAs in 67 human left ventricular samples belonging to control ( n = 10), ischemic cardiomyopathy (ICM, n = 19), dilated cardiomyopathy (DCM, n = 25), or aortic stenosis (AS, n = 13) diagnostic groups. miRNA expression between disease and control groups was compared by ANOVA with Dunnett's post hoc test. We controlled for multiple testing by estimating the false discovery rate. Out of 428 microRNAs measured, 87 were confidently detected; 43 were differentially expressed in at least one disease group. In supervised clustering, microRNA expression profiles correctly grouped samples by their clinical diagnosis, indicating that microRNA expression profiles are distinct between diagnostic groups. This was further supported by class prediction approaches, in which the class (control, ICM, DCM, AS) predicted by a microRNA-based classifier matched the clinical diagnosis 69% of the time ( P < 0.001). These data show that expression of many microRNAs is altered in heart disease and that different types of heart disease are associated with distinct changes in microRNA expression. These data will guide further studies of the contribution of microRNAs to heart disease pathogenesis.
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Segura-Wang, Maia, Bertrand Grenier, Suzana Ilic, Ursula Ruczizka, Maximiliane Dippel, Moritz Bünger, Matthias Hackl i Veronika Nagl. "MicroRNA Expression Profiling in Porcine Liver, Jejunum and Serum upon Dietary DON Exposure Reveals Candidate Toxicity Biomarkers". International Journal of Molecular Sciences 22, nr 21 (7.11.2021): 12043. http://dx.doi.org/10.3390/ijms222112043.
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Deoxynivalenol (DON), a frequent mycotoxin worldwide, impairs human and animal health. The response of microRNAs, small non-coding RNAs, to DON has been scarcely investigated, but holds remarkable potential for biomarker applications. Hence, we aimed to investigate DON-induced changes in the microRNA expression in porcine liver, jejunum and serum by combining targeted and untargeted analyses. Piglets received uncontaminated feed or feed containing 900 µg/kg and 2500 µg/kg DON for four weeks, followed by a wash-out period. In tissue, only slight changes in microRNA expression were detected, with ssc-miR-10b being downregulated in liver of DON-exposed piglets. In serum, several microRNAs were differentially expressed upon DON exposure, four of which were validated by qPCR (ssc-miR-16, ssc-miR-128, ssc-miR-451, ssc-miR-205). The serum microRNA response to DON increased over time and declined after removal of contaminated diets. Receiver operating curve analyses for individual microRNAs were significant, and a combination of the four microRNAs increased the predictive capacity for DON exposure. Predicted microRNA target genes showed enrichment of several pathways including PIK3-AKT, Wnt/β-catenin, and adherens junctions. This study gives, for the first time, a comprehensive view of the porcine microRNA response to DON, providing a basis for future research on microRNAs as biomarkers for mycotoxins.
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Zhang, Jenny, Dereje D. Jima, Cassandra Jacobs, Randy Fischer, Eva Gottwein, Grace Huang, Patricia L. Lugar i in. "Patterns of microRNA expression characterize stages of human B-cell differentiation". Blood 113, nr 19 (7.05.2009): 4586–94. http://dx.doi.org/10.1182/blood-2008-09-178186.
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Abstract Mature B-cell differentiation provides an important mechanism for the acquisition of adaptive immunity. Malignancies derived from mature B cells constitute the majority of leukemias and lymphomas. These malignancies often maintain the characteristics of the normal B cells that they are derived from, a feature that is frequently used in their diagnosis. The role of microRNAs in mature B cells is largely unknown. Through concomitant microRNA and mRNA profiling, we demonstrate a potential regulatory role for microRNAs at every stage of the mature B-cell differentiation process. In addition, we have experimentally identified a direct role for the microRNA regulation of key transcription factors in B-cell differentiation: LMO2 and PRDM1 (Blimp1). We also profiled the microRNA of B-cell tumors derived from diffuse large B-cell lymphoma, Burkitt lymphoma, and chronic lymphocytic leukemia. We found that, in contrast to many other malignancies, common B-cell malignancies do not down-regulate microRNA expression. Although these tumors could be distinguished from each other with use of microRNA expression, each tumor type maintained the expression of the lineage-specific microRNAs. Expression of these lineage-specific microRNAs could correctly predict the lineage of B-cell malignancies in more than 95% of the cases. Thus, our data demonstrate that microRNAs may be important in maintaining the mature B-cell phenotype in normal and malignant B cells.
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Zhang, Zhen-Zhen, Heng-Chang Cao, Dong-Li Huang, Qi Wu, Xiao-Fan Chen, Jun Wan i Wei Zhang. "MicroRNA-200c plays an oncogenic role in nasopharyngeal carcinoma by targeting PTEN". Tumor Biology 39, nr 5 (maj 2017): 101042831770365. http://dx.doi.org/10.1177/1010428317703655.
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Recent studies suggested that microRNA-200 family microRNAs play critical roles in cancer initiation and metastasis. The underlying mechanism remained elusive. In this study, we show that microRNA-200c is upregulated in nasopharyngeal carcinoma cells. Manipulation of microRNA-200c levels affected cell growth, migration, and invasion in nasopharyngeal carcinoma cell lines. Furthermore, PTEN was identified as a direct target of microRNA-200c. Overexpression of PTEN resulted in similar effects to those of anti-microRNA-200c transfection. In vivo suppression of microRNA-200c level reduced tumor growth in mice. Overall, our data suggest that microRNA-200c plays an oncogenic role in nasopharyngeal carcinoma by targeting PTEN.
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van den Homberg, Daphne A. L., Reginald V. C. T. van der Kwast, Paul H. A. Quax i A. Yaël Nossent. "N-6-Methyladenosine in Vasoactive microRNAs during Hypoxia; A Novel Role for METTL4". International Journal of Molecular Sciences 23, nr 3 (19.01.2022): 1057. http://dx.doi.org/10.3390/ijms23031057.
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N-6-methyladenosine (m6A) is the most prevalent post-transcriptional RNA modification in eukaryotic cells. The modification is reversible and can be dynamically regulated by writer and eraser enzymes. Alteration in the levels of these enzymes can lead to changes in mRNA stability, alternative splicing or microRNA processing, depending on the m6A-binding proteins. Dynamic regulation of mRNA m6A methylation after ischemia and hypoxia influences mRNA stability, alternative splicing and translation, contributing to heart failure. In this study, we studied vasoactive microRNA m6A methylation in fibroblasts and examined the effect of hypoxia on microRNAs methylation using m6A immunoprecipitation. Of the 19 microRNAs investigated, at least 16 contained m6A in both primary human fibroblasts and a human fibroblast cell line, suggesting vasoactive microRNAs are commonly m6A methylated in fibroblasts. More importantly, we found that mature microRNA m6A levels increased upon subjecting cells to hypoxia. By silencing different m6A writer and eraser enzymes followed by m6A immunoprecipitation, we identified METTL4, an snRNA m6A methyltransferase, to be predominantly responsible for the increase in m6A modification. Moreover, by using m6A-methylated microRNA mimics, we found that microRNA m6A directly affects downstream target mRNA repression efficacy. Our findings highlight the regulatory potential of the emerging field of microRNA modifications.
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Robertson, Stacy, Louise A. Diver, Samantha Alvarez-Madrazo, Craig Livie, Ayesha Ejaz, Robert Fraser, John M. Connell, Scott M. MacKenzie i Eleanor Davies. "Regulation of Corticosteroidogenic Genes by MicroRNAs". International Journal of Endocrinology 2017 (9.08.2017): 1–11. http://dx.doi.org/10.1155/2017/2021903.
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The loss of normal regulation of corticosteroid secretion is important in the development of cardiovascular disease. We previously showed that microRNAs regulate the terminal stages of corticosteroid biosynthesis. Here, we assess microRNA regulation across the whole corticosteroid pathway. Knockdown of microRNA using Dicer1 siRNA in H295R adrenocortical cells increased levels of CYP11A1, CYP21A1, and CYP17A1 mRNA and the secretion of cortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycorticosterone, and aldosterone. Bioinformatic analysis of genes involved in corticosteroid biosynthesis or metabolism identified many putative microRNA-binding sites, and some were selected for further study. Manipulation of individual microRNA levels demonstrated a direct effect of miR-125a-5p and miR-125b-5p on CYP11B2 and of miR-320a-3p levels on CYP11A1 and CYP17A1 mRNA. Finally, comparison of microRNA expression profiles from human aldosterone-producing adenoma and normal adrenal tissue showed levels of various microRNAs, including miR-125a-5p to be significantly different. This study demonstrates that corticosteroidogenesis is regulated at multiple points by several microRNAs and that certain of these microRNAs are differentially expressed in tumorous adrenal tissue, which may contribute to dysregulation of corticosteroid secretion. These findings provide new insights into the regulation of corticosteroid production and have implications for understanding the pathology of disease states where abnormal hormone secretion is a feature.
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Kriegel, Alison J., Domagoj Mladinov i Mingyu Liang. "Translational study of microRNAs and its application in kidney disease and hypertension research". Clinical Science 122, nr 10 (20.01.2012): 439–47. http://dx.doi.org/10.1042/cs20110159.
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MicroRNA research in humans and mammalian model organisms is in a crucial stage of development. Diagnostic and therapeutic values of microRNAs appear promising, but remain to be established. The physiological and pathophysiological significance of microRNAs is generally recognized, but much better understood in some organ systems and disease areas than others. In the present paper, we review several translational studies of microRNAs, including those showing the potential value of therapeutic agents targeting microRNAs and diagnostic or prognostic microRNA markers detectable in body fluids. We discuss the lessons learned and the experience gained from these studies. Several recent studies have begun to explore translational microRNA research in kidney disease and hypertension. Translational research of microRNAs in the kidney faces unique challenges, but provides many opportunities to develop and apply new methods, and to merge complementary basic and clinical approaches.
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Dhayat, Sameer, Max Traeger, Jan Rehkaemper, Anda Stroese, Konrad Steinestel, Eva Wardelmann, Iyad Kabar i Norbert Senninger. "Clinical Impact of Epithelial-to-Mesenchymal Transition Regulating MicroRNAs in Pancreatic Ductal Adenocarcinoma". Cancers 10, nr 9 (13.09.2018): 328. http://dx.doi.org/10.3390/cancers10090328.
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Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive carcinoma entities worldwide with early and rapid dissemination. Recently, we discussed the role of microRNAs as epigenetic regulators of Epithelial-to-Mesenchymal Transition (EMT) in PDAC. In this study, we investigated their value as diagnostic and prognostic markers in tissue and blood samples of 185 patients including PDAC, non-malignant pancreatic disorders, and age-matched healthy controls. Expression of the microRNA-200-family (microRNAs -141, -200a, -200b, -200c, -429) and microRNA-148a was significantly downregulated in tissue of PDAC Union internationale contre le cancer (UICC) Stage II. Correspondingly, stromal PDAC tissue showed strong expression of Fibronectin, Vimentin, and ZEB-1 (Zinc finger E-box-binding homeobox) versus low expression of E-cadherin. Transient transfection of microRNA-200b and microRNA-200c mimics resulted in the downregulation of their key target ZEB-1. Inversely, blood serum analyses of patients with PDAC UICC Stages II, III, and IV showed a significant over-expression of microRNA-200-family members, microRNA-148a, microRNA-10b, and microRNA-34a. Correspondingly, Enzyme-linked Immunosorbent Assay (ELISA) analyses revealed a significant over-expression of soluble E-cadherin in serum samples of PDAC patients versus healthy controls. The best diagnostic accuracy to distinguish between PDAC and non-PDAC in this patient collective could be achieved in tissue by microRNA-148a with an area under the receiver-operating-characteristic (ROC) curve (AUC) of 0.885 and in blood serum by a panel of microRNA-141, -200b, -200c, and CA.19-9 with an AUC of 0.890. Both diagnostic tools outreach the diagnostic performance of the currently most common diagnostic biomarker CA.19-9 (AUC of 0.834). Kaplan Meier survival analysis of this patient collective revealed an improved overall survival in PDAC patients with high expression of tissue-related microRNA-34a, -141, -200b, -200c, and -429. In conclusion, EMT-regulating microRNAs have great potential as liquid and solid biopsy markers in PDAC patients. Their prognostic and therapeutic benefits remain important tasks for future studies.
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Lopez, Mary S., Robert J. Dempsey i Raghu Vemuganti. "Resveratrol preconditioning induces cerebral ischemic tolerance but has minimal effect on cerebral microRNA profiles". Journal of Cerebral Blood Flow & Metabolism 36, nr 9 (21.07.2016): 1644–50. http://dx.doi.org/10.1177/0271678x16656202.
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The health benefits of the plant-derived polyphenol resveratrol were established in multiple disease systems. Notably, pre-treatment with resveratrol was shown to be neuroprotective in several models of cerebral ischemia. Mechanisms of resveratrol-mediated neuroprotection have been explored in the context of canonical resveratrol targets, but epigenetic and non-coding RNA processes have not yet been evaluated. Resveratrol was shown to alter microRNAs in cancer and cardiac ischemia. Previous studies also showed that ischemic preconditioning that induces ischemic tolerance significantly alters cerebral microRNA levels, particularly those that target neuroprotective pathways. Therefore, we tested if resveratrol-mediated ischemic tolerance also alters microRNA expression with a goal to identify microRNAs that are amenable to manipulation to induce neuroprotection after cerebral ischemia. Hence, we tested the microRNA profiles in mouse brain following intraperitoneal administration of resveratrol that induced significant tolerance against transient focal ischemia. We analyzed microRNA profiles using microarrays from both Affymetrix and LC Sciences that contain probes for all known mouse microRNAs. The results show that there is no consistent change in any of the microRNAs tested between resveratrol and vehicle groups indicating that microRNAs play a minimal role in resveratrol-mediated cerebral ischemic tolerance.
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Malumbres, Raquel, Robert Tibshirani, Elena Cubedo, Kristopher A. Sarosiek, Xiaoyu Jiang, Jose Ruiz i Izidore Lossos. "Differentiation-Stage-Specific Expression of MicroRNAs in B-Lymphocytes and Diffuse Large B-Cell Lymphomas (DLBCL)". Blood 112, nr 11 (16.11.2008): 805. http://dx.doi.org/10.1182/blood.v112.11.805.805.
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Abstract B-cell development and differentiation are complex processes controlled by distinct programs of transcriptional control. A large set of transcriptional factors together or in succession control this process and their deregulation may result in block of differentiation or malignant transformation. MicroRNAs are small RNAs that orchestrate cellular functions by modulating the level of their targeted proteins by either translational arrest or transcript degradation, and play a key role in cell differentiation, apoptosis, proliferation and cancer development. An increasing number of transcription factors are being found targeted by microRNAs. Emerging evidence suggests that differentiation stage-specific expression of microRNAs occurs in the hematopoietic system and during T cell differentiation. Only limited information exists on microRNA expression in normal B cell differentiation and its malignant counterparts. Herein we analyzed microRNA expression profiles in distinct peripheral B cell differentiation stages-naïve, germinal center (GC) centroblasts and memory cells as well as tonsilar T cells. Furthermore, microRNA profiling was performed in germinal center-like (GCB-like) and activated B-cell-like (ABC-like) DLBCL cell lines originating from distinct B-cell differentiation stages. RNA, extracted with mirVana kit (AMBION) from B cell subsets and T cells enriched from normal tonsils was hybridized on LC Sciences (Houston, TX) microarrays harboring 470 human microRNAs probes (Sanger miRBase Release 9.1). Expression of selected microRNAs was confirmed by ABI RT-PCR methodology. Unsupervised clustering of microRNAs with values present in at least 50% of the samples (122 probes) resulted in perfect differentiation-stage clustering of samples. Application of Statistical Analysis of Microarrays (SAM) and Prediction Analysis of Microarrays (PAM) methods (FDR= 10%) identified a 47 microRNA cell of origin classifier for B-cells differentiation stage; 27 of these microRNAs were upregulated and 20 downregulated in centroblasts compared to memory B-cells. MicroRNAs belonging to paralog microRNA clusters (e.g. miR17-92-1, miR363-106a and miR25-106b) demonstrated similar patterns of expression in specific differentiation stages. To identify specific microRNA targets, miRanda, TargetScan and PicTar programs were used. To experimentally confirm the targets, we assessed the effects of specific microRNAs on the expression levels of targeted proteins and on the luciferase reporter under the control of the wild type and mutated 3′ UTR regions of putative target genes. Using this experimental approach we identified lymphocyte-stage-specific microRNAs which expression inversely correlated and might regulate the expression of LMO2, BLIMP1 and IRF4 proteins distinctively expressed at different differentiation stages of B lymphocytes. For example, miR223, which expression is low in GC cells but is high in naïve and memory B cells, downregulates the expression of LMO2. We next analyzed microRNA expression in DLBCL cell lines. Clustering analysis, using the 47 microRNA cell of origin classifier perfectly classified GCB-like and ABC-like cell lines. Interestingly, the expression of microRNAs in both GCB-like and ABC-like DLBCL cell lines was more similar to normal centroblasts than to memory B cells, suggesting that both may originate from distinct subpopulations of GC lymphocytes. The similarity of microRNA expression in cell lines to centroblasts was striking, with only 16 microRNAs (1 upregulated and 15 downregulated in cell lines) showing noticeable differences in levels of expression compared to normal cells. These microRNAs might be involved in the process of lymphoma transformation. SAM analysis aimed to differentiate GCB-like and ABC-like cell lines identified 11 microRNAs, only 3 of which were present in the cell of origin classifier. This observation suggests that there is also a difference in expression of microRNAs not directly related to the distinct cell of origin between the DLBCL subtypes. In summary, our results demonstrate that the microRNA profile changes during the GC reaction as well as during malignant transformation. Specific microRNAs can regulate key transcription factors controlling the processes of lymphocyte differentiation and transformation.
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Manasa, VG, i S. Kannan. "Impact of microRNA dynamics on cancer hallmarks: An oral cancer scenario". Tumor Biology 39, nr 3 (marzec 2017): 101042831769592. http://dx.doi.org/10.1177/1010428317695920.
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MicroRNAs are endogenous small noncoding RNAs that negatively regulate gene expression at posttranscriptional level. The discovery of microRNAs has identified a new layer of gene regulation mechanisms, which play a pivotal role in development as well as in various cellular processes, such as proliferation, differentiation, cell growth, and cell death. Deregulated microRNA expression favors acquisition of cancer hallmark traits as well as transforms the tumor microenvironment, leading to tumor development and progression. Many recent studies have revealed altered expression of microRNAs in oral carcinoma with several microRNAs shown to have key biological role in tumorigenesis functioning either as tumor suppressors or as tumor promoters. MicroRNA expression levels correlate with clinicopathological variables and have a diagnostic and prognostic value in oral carcinoma. For these reasons, microRNA has been a hot topic in oral cancer research for the last few years. In this review, we attempt to summarize the present understanding of microRNA deregulation in oral carcinoma, their role in acquiring cancer hallmarks, and their potential diagnostic and prognostic value for oral cancer management.
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Pérez-Carrillo, Lorena, Isaac Giménez-Escamilla, María García-Manzanares, Juan Carlos Triviño, Sandra Feijóo-Bandín, Alana Aragón-Herrera, Francisca Lago i in. "Altered MicroRNA Maturation in Ischemic Hearts: Implication of Hypoxia on XPO5 and DICER1 Dysregulation and RedoximiR State". Antioxidants 12, nr 7 (24.06.2023): 1337. http://dx.doi.org/10.3390/antiox12071337.
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Ischemic cardiomyopathy (ICM) is associated with abnormal microRNA expression levels that involve an altered gene expression profile. However, little is known about the underlying causes of microRNA disruption in ICM and whether microRNA maturation is compromised. Therefore, we focused on microRNA maturation defects analysis and the implication of the microRNA biogenesis pathway and redox-sensitive microRNAs (redoximiRs). Transcriptomic changes were investigated via ncRNA-seq (ICM, n = 22; controls, n = 8) and mRNA-seq (ICM, n = 13; control, n = 10). The effect of hypoxia on the biogenesis of microRNAs was evaluated in the AC16 cell line. ICM patients showed a reduction in microRNA maturation compared to control (4.30 ± 0.94 au vs. 5.34 ± 1.07 au, p ˂ 0.05), accompanied by a deregulation of the microRNA biogenesis pathway: a decrease in pre-microRNA export (XPO5, FC = −1.38, p ˂ 0.05) and cytoplasmic processing (DICER, FC = −1.32, p ˂ 0.01). Both processes were regulated by hypoxia in AC16 cells (XPO5, FC = −1.65; DICER1, FC = −1.55; p ˂ 0.01; Exportin-5, FC = −1.81; Dicer, FC = −1.15; p ˂ 0.05). Patients displayed deregulation of several redoximiRs, highlighting miR-122-5p (FC = −2.41, p ˂ 0.001), which maintained a good correlation with the ejection fraction (r = 0.681, p ˂ 0.01). We evidenced a decrease in microRNA maturation mainly linked to a decrease in XPO5-mediated pre-microRNA export and DICER1-mediated processing, together with a general effect of hypoxia through deregulation of biogenesis pathway and the redoximiRs.
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Xu, Junhua, John Linneman, Yanfeng Zhong, Haoyang Yin, Qinyi Xia, Kang Kang i Deming Gou. "MicroRNAs in Pulmonary Hypertension, from Pathogenesis to Diagnosis and Treatment". Biomolecules 12, nr 4 (24.03.2022): 496. http://dx.doi.org/10.3390/biom12040496.
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Pulmonary hypertension (PH) is a fatal and untreatable disease, ultimately leading to right heart failure and eventually death. microRNAs are small, non-coding endogenous RNA molecules that can regulate gene expression and influence various biological processes. Changes in microRNA expression levels contribute to various cardiovascular disorders, and microRNAs have been shown to play a critical role in PH pathogenesis. In recent years, numerous studies have explored the role of microRNAs in PH, focusing on the expression profiles of microRNAs and their signaling pathways in pulmonary artery smooth muscle cells (PASMCs) or pulmonary artery endothelial cells (PAECs), PH models, and PH patients. Moreover, certain microRNAs, such as miR-150 and miR-26a, have been identified as good candidates of diagnosis biomarkers for PH. However, there are still several challenges for microRNAs as biomarkers, including difficulty in normalization, specificity in PH, and a lack of longitudinal and big sample-sized studies. Furthermore, microRNA target drugs are potential therapeutic agents for PH treatment, which have been demonstrated in PH models and in humans. Nonetheless, synthetic microRNA mimics or antagonists are susceptible to several common defects, such as low drug efficacy, inefficient drug delivery, potential toxicity and especially, off-target effects. Therefore, finding clinically safe and effective microRNA drugs remains a great challenge, and further breakthrough is urgently needed.
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Abaturov, A. E., i V. L. Babуch. "Regulation of microRNA with food. Part 2. Food of animal origin". CHILD`S HEALTH 18, nr 7 (7.12.2023): 536–43. http://dx.doi.org/10.22141/2224-0551.18.7.2023.1647.
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The scientific review considers the mechanisms of microRNA regulation of biological processes in the human body with the help of food products, namely those of animal origin. To write the article, information was searched using Scopus, Web of Science, MEDLINE, PubMed, Google Scholar, Embase, Global Health, The Cochrane Library databases. It is known that microRNA molecules of milk retain their biological activity in the digestive tract for a long time, reach the intestinal mucosa and penetrate the internal continuum of the body. It is stated that in breast milk, microRNAs are mainly found in extracellular vesicles, which are signalosomes that mediate the effectiveness of molecular communication between the mother and her child. Breast milk has been shown to contain about 1,400 different miRNAs, most of which are located in exosomes. The authors indicate that the representation of miRNA in breast milk changes during the postpartum period. Scientists believe that large amounts of microRNAs are found both in raw cow’s milk and in commercial dairy foods. Formulas are miRNA-deficient dairy foods. The authors provide data that miR-148a deficiency is associated with the development of pathological processes of the hepatobiliary system such as inflammation, liver fibrosis, carcinogenesis and lipid metabolism disorders. It has been shown that meat products contain large amounts of various miRNAs, which can retain their functional activity even after heat treatment. So, in a comprehensive review using the latest information search databases, it was found that in the modern scientific literature, the authors determine the horizontal transfer of numerous microRNA molecules from animals to the human body. The main food product that restores microRNA deficiency is milk. Breast milk contains mRNA, microRNA and many other active substances. Feeding children with formulas leads to a pronounced deficiency of exogenous miRNAs. The change in the structure of the human transcriptome is due to the consumption of meat products.