Journal articles on the topic 'Microrna targets'
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Baxter, Diana E., Lisa M. Allinson, Waleed S. Al Amri, James A. Poulter, Arindam Pramanik, James L. Thorne, Eldo T. Verghese, and Thomas A. Hughes. "MiR-195 and Its Target SEMA6D Regulate Chemoresponse in Breast Cancer." Cancers 13, no. 23 (November 28, 2021): 5979. http://dx.doi.org/10.3390/cancers13235979.
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Background: poor prognosis primary breast cancers are typically treated with cytotoxic chemotherapy. However, recurrences remain relatively common even after this aggressive therapy. Comparison of matched tumours pre- and post-chemotherapy can allow identification of molecular characteristics of therapy resistance and thereby potentially aid discovery of novel predictive markers or targets for chemosensitisation. Through this comparison, we aimed to identify microRNAs associated with chemoresistance, define microRNA target genes, and assess targets as predictors of chemotherapy response. Methods: cancer cells were laser microdissected from matched breast cancer tissues pre- and post-chemotherapy from estrogen receptor positive/HER2 negative breast cancers showing partial responses to epirubicin/cyclophosphamide chemotherapy (n = 5). MicroRNA expression was profiled using qPCR arrays. MicroRNA/mRNA expression was manipulated in estrogen receptor positive/HER2 negative breast cancer cell lines (MCF7 and MDA-MB-175 cells) with mimics, inhibitors or siRNAs, and chemoresponse was assessed using MTT and colony forming survival assays. MicroRNA targets were identified by RNA-sequencing of microRNA mimic pull-downs, and comparison of these with mRNAs containing predicted microRNA binding sites. Survival correlations were tested using the METABRIC expression dataset (n = 1979). Results: miR-195 and miR-26b were consistently up-regulated after therapy, and changes in their expression in cell lines caused significant differences in chemotherapy sensitivity, in accordance with up-regulation driving resistance. SEMA6D was defined and confirmed as a target of the microRNAs. Reduced SEMA6D expression was significantly associated with chemoresistance, in accordance with SEMA6D being a down-stream effector of the microRNAs. Finally, low SEMA6D expression in breast cancers was significantly associated with poor survival after chemotherapy, but not after other therapies. Conclusions: microRNAs and their targets influence chemoresponse, allowing the identification of SEMA6D as a predictive marker for chemotherapy response that could be used to direct therapy or as a target in chemosensitisation strategies.
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Huang, Tinghua, Xiali Huang, and Min Yao. "Min3: Predict microRNA target gene using an improved binding-site representation method and support vector machine." Journal of Bioinformatics and Computational Biology 17, no. 05 (October 2019): 1950032. http://dx.doi.org/10.1142/s021972001950032x.
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MicroRNAs are single-stranded noncoding RNAs known to down-regulate target genes at the protein or mRNA level. Computational prediction of targets is essential for elucidating the detailed functions of microRNA. However, prediction specificity and sensitivity of the existing algorithms still need to be improved to generate useful hypotheses for subsequent experimental testing. A new microRNA binding-site representation method was developed, which uses four symbols “[Formula: see text]”, “:”, “[Formula: see text]”, and “[Formula: see text]” (indicating paired, unpaired, insertion, and bulge, respectively) to represent the status of each nucleotide base pair in the microRNA binding site. New features were established with the information of every two adjacent symbols. There are 12 possible combinations and the frequency of each defines a set of novel and useful features. A comprehensive training dataset is constructed for mammalian microRNAs with positive targets obtained from the microRNA target depository in the miRTarbase, while negative targets were derived from pseudo-microRNA bindings. An SVM model was established using the training dataset and a new software called Min3 was developed. Performance of Min3 was assessed with intensively studied examples of miR-155 and miR-92a. Prediction results showed that Min3 can discover 47% of experimental conformed targets on average. The overlapping is above 20% on average when compared with TargetScan and miRanda. Annotations of the public microRNA datasets showed that there is a negative effect (up-regulation) of the Min3 targets for the knock out/down of miR-155 and miR-92a. Six top ranked targets were selected for validation by wet-lab experiments, and five of them showed a regulation effect. The Min3 can be a good alternative to current microRNA target discovery software. This tool is available at https://sourceforge.net/projects/mirt3 .
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Arora, Amit. "MicroRNA targets." Pharmacogenetics and Genomics 25, no. 3 (March 2015): 107–25. http://dx.doi.org/10.1097/fpc.0000000000000111.
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Torkey, Hanaa, Lenwood S. Heath, and Mahmoud ElHefnawi. "MicroTarget: MicroRNA target gene prediction approach with application to breast cancer." Journal of Bioinformatics and Computational Biology 15, no. 04 (August 2017): 1750013. http://dx.doi.org/10.1142/s0219720017500135.
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MicroRNAs are known to play an essential role in gene regulation in plants and animals. The standard method for understanding microRNA–gene interactions is randomized controlled perturbation experiments. These experiments are costly and time consuming. Therefore, use of computational methods is essential. Currently, several computational methods have been developed to discover microRNA target genes. However, these methods have limitations based on the features that are used for prediction. The commonly used features are complementarity to the seed region of the microRNA, site accessibility, and evolutionary conservation. Unfortunately, not all microRNA target sites are conserved or adhere to exact seed complementary, and relying on site accessibility does not guarantee that the interaction exists. Moreover, the study of regulatory interactions composed of the same tissue expression data for microRNAs and mRNAs is necessary to understand the specificity of regulation and function. We developed MicroTarget to predict a microRNA–gene regulatory network using heterogeneous data sources, especially gene and microRNA expression data. First, MicroTarget employs expression data to learn a candidate target set for each microRNA. Then, it uses sequence data to provide evidence of direct interactions. MicroTarget scores and ranks the predicted targets based on a set of features. The predicted targets overlap with many of the experimentally validated ones. Our results indicate that using expression data in target prediction is more accurate in terms of specificity and sensitivity. Available at: https://bioinformatics.cs.vt.edu/~htorkey/microTarget .
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Smoczynska, Aleksandra, Andrzej M. Pacak, Przemysław Nuc, Aleksandra Swida-Barteczka, Katarzyna Kruszka, Wojciech M. Karlowski, Artur Jarmolowski, and Zofia Szweykowska-Kulinska. "A Functional Network of Novel Barley MicroRNAs and Their Targets in Response to Drought." Genes 11, no. 5 (April 29, 2020): 488. http://dx.doi.org/10.3390/genes11050488.
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The regulation of mRNA (messenger RNA) levels by microRNA-mediated activity is especially important in plant responses to environmental stresses. In this work, we report six novel barley microRNAs, including two processed from the same precursor that are severely downregulated under drought conditions. For all analyzed microRNAs, we found target genes that were upregulated under drought conditions and that were known to be involved in a plethora of processes from disease resistance to chromatin–protein complex formation and the regulation of transcription in mitochondria. Targets for novel barley microRNAs were confirmed through degradome data analysis and RT-qPCR using primers flanking microRNA-recognition site. Our results show a broad transcriptional response of barley to water deficiency conditions through microRNA-mediated gene regulation and facilitate further research on drought tolerance in crops.
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Ma, Xiao, Dan Li, Yan Gao, and Cheng Liu. "miR-451a Inhibits the Growth and Invasion of Osteosarcoma via Targeting TRIM66." Technology in Cancer Research & Treatment 18 (January 1, 2019): 153303381987020. http://dx.doi.org/10.1177/1533033819870209.
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The importance of microRNAs in regulating osteosarcoma development has been studied in recent years. However, the function of microRNA-451a in osteosarcoma growth is rarely investigated. Here, we explored the expression of microRNA-451a in osteosarcoma cell lines. Bioinformatic software, luciferase activity reporter assay, and Western blot were conducted to determine the association between microRNA-451a and tripartite motif-containing 66. Cell Counting Kit-8 assay and transwell assay were used to explore the regulatory effects of microRNA-451a on osteosarcoma cells. Moreover, we explored whether microRNA-451a modulates osteosarcoma cell biological activity by regulating tripartite motif-containing 66. The expression of microRNA-451a was found to be downregulated in osteosarcoma and negatively regulated the expression of tripartite motif-containing 66. Tripartite motif-containing 66 was further validated as a target of microRNA-451a. MicroRNA-451a inhibits the growth and invasion of osteosarcoma cell lines through targeting tripartite motif-containing 66. The miR-451a targets tripartite motif-containing 66 may provide novel therapeutic targets for the treatment of osteosarcoma.
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Chu, W. H., L. Harland, P. Grant, M. De Blasio, W. Kong, S. Moretta, J. S. Robinson, M. E. Dziadek, and J. A. Owens. "163. MATERNAL FOLIC ACID SUPPLEMENTATION INDUCED ALTERATIONS IN METABOLIC HEALTH OF PROGENY: ROLE OF microRNA REGULATORY NETWORKS." Reproduction, Fertility and Development 21, no. 9 (2009): 81. http://dx.doi.org/10.1071/srb09abs163.
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Background: Nutrition in early life can influence metabolic functionality in later life, in part via heritable epigenetic changes, which modify gene expression without altering DNA sequence. Folate supplies methyl groups for the methylation of DNA and histones, both major epigenetic marks that change dynamically in utero. We have recently shown that maternal folic acid supplementation (MFAS) in the pregnant rat increases insulin sensitivity in adult male progeny, while decreasing that of females. The molecular basis of this is unknown but microRNAs may play a role. MicroRNAs are epigenetically regulated non-coding RNAs that downregulate post-transcriptional expression of their targets. MFAS may modulate epigenetics and expression of microRNAs and their targets in adult progeny to alter insulin sensitivity. Aims/Hypotheses: The effect of MFAS before and throughout pregnancy on microRNA expression in liver and skeletal muscle of adult progeny was determined. Methods: Female Wistar rats were fed Control (n=11) or Folic Acid Supplemented (n=9) diets containing either 2 or 6 mg folic acid/kg respectively, from two weeks before mating and throughout pregnancy. One male and female progeny per litter were sacrificed on postnatal day 90 and microRNA expression was determined by Exiqon microRNA microarray v.8.1. Results: MFAS altered hepatic microRNA expression in adult male progeny, but did not alter that in females. Sixteen hepatic microRNAs were differentially expressed, with five predicted in silico (rno-miR: 23a, 23b, 212, 298 and 325-5p) to target several key insulin signalling molecules (p85α, p110β, Akt2, and Prkcz). miR-122a, which promotes cholesterol and lipid synthesis in vivo, was also downregulated. MFAS did not alter microRNA expression in skeletal muscle of adult male or female progeny. Conclusions: MFAS alters hepatic microRNA expression in adult male progeny. Changes in their expression together with their targets in insulin signalling pathway may initiate increased insulin sensitivity in adult male progeny.
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John, Bino, Anton J. Enright, Alexei Aravin, Thomas Tuschl, Chris Sander, and Debora S. Marks. "Human MicroRNA Targets." PLoS Biology 2, no. 11 (October 5, 2004): e363. http://dx.doi.org/10.1371/journal.pbio.0020363.
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Da Costa Martins, Paula A., and Leon J. De Windt. "Targeting MicroRNA Targets." Circulation Research 111, no. 5 (August 17, 2012): 506–8. http://dx.doi.org/10.1161/circresaha.112.276717.
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Seitz, Hervé. "Redefining MicroRNA Targets." Current Biology 19, no. 10 (May 2009): 870–73. http://dx.doi.org/10.1016/j.cub.2009.03.059.
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Jayaseelan, Vijayashree Priyadharsini, and Paramasivam Arumugam. "Exosomal microRNAs Targeting TP53 Gene as Promising Prognostic Markers for Head and Neck Squamous Cell Carcinoma." Global Medical Genetics 09, no. 04 (December 2022): 277–86. http://dx.doi.org/10.1055/s-0042-1758204.
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Abstract Statement of Problem MicroRNAs are small non-coding RNAs that regulate an array of functions by targeting crucial genes. A significant dysregulation in the TP53 profile has been observed in the head and neck squamous cell carcinoma (HNSCC) patients. Hence, the present in silico study was designed to identify those microRNAs which target TP53 gene and demonstrate their differential expression in HNSCC cases. Materials and Methods The study was extended further to explore their exosomal location using database such as EVmiRNA and ExoCarta. The study follows an observational in silico design. Computational tool miRDB was used identify the microRNA targets of TP53 gene. The UALCAN server was used to ascertain the expression of microRNA in HNSCC cases derived from the Cancer Gene Atlas dataset. The survival of HNSCC patients based on the differential expression microRNA markers were recorded. Further, each of the microRNA was queried for their exosomal presence using EVmiRNA. Results About 102 microRNA targets of TP53 gene with a target score in the range of 95–50 were identified. The differential expression data for 52 microRNAs was retrieved from the UALCAN database. The microRNAs hsa-miR-421, hsa-miR-548f-5p, and hsa-let-7c-5p were found to be differentially expressed with marked influence over the survival of HNSCC patients. Furthermore, hsa-miR-421 and hsa-let-7c-5p were found to have an exosomal origin especially in body fluids such as blood and saliva. Conclusion The results accumulated from the present study identified three microRNAs which can affect the functions of TP53 gene and bring about serious outcomes in HNSCC patients. The microRNAs of exosomal origin targeting TP53 gene in HNSCC patients can be a promising prognostic marker, which can be further used as a therapeutic lead by designing inhibitors.
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Rana, Indrajeetsinh, Elena Velkoska, Sheila K. Patel, Louise M. Burrell, and Fadi J. Charchar. "MicroRNAs mediate the cardioprotective effect of angiotensin-converting enzyme inhibition in acute kidney injury." American Journal of Physiology-Renal Physiology 309, no. 11 (December 1, 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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Ørom, Ulf Andersson, and Anders H. Lund. "Isolation of microRNA targets using biotinylated synthetic microRNAs." Methods 43, no. 2 (October 2007): 162–65. http://dx.doi.org/10.1016/j.ymeth.2007.04.007.
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Yousef, Malik, Segun Jung, Andrew V. Kossenkov, Louise C. Showe, and Michael K. Showe. "Naïve Bayes for microRNA target predictions—machine learning for microRNA targets." Bioinformatics 23, no. 22 (October 8, 2007): 2987–92. http://dx.doi.org/10.1093/bioinformatics/btm484.
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Trinidad-Barnech, Juan Manuel, Rafael Sebastián Fort, Guillermo Trinidad Barnech, Beatriz Garat, and María Ana Duhagon. "Transcriptome-Wide Analysis of microRNA–mRNA Correlations in Tissue Identifies microRNA Targeting Determinants." Non-Coding RNA 9, no. 1 (February 13, 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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Cihan, Mert, and Miguel A. Andrade-Navarro. "Detection of features predictive of microRNA targets by integration of network data." PLOS ONE 17, no. 6 (June 9, 2022): e0269731. http://dx.doi.org/10.1371/journal.pone.0269731.
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Gene activity is controlled by multiple molecular mechanisms, for instance through transcription factors or by microRNAs (miRNAs), among others. Established bioinformatics tools for the prediction of miRNA target genes face the challenge of ensuring accuracy, due to high false positive rates. Further, these tools present poor overlap. However, we demonstrated that it is possible to filter good predictions of miRNA targets from the bulk of all predictions by using information from the gene regulatory network. Here, we take advantage of this strategy that selects a large subset of predicted microRNA binding sites as more likely to possess less false-positives because of their over-representation in RE1 silencing transcription factor (REST)-regulated genes from the background of TargetScanHuman 7.2 predictions to identify useful features for the prediction of microRNA targets. These enriched miRNA families would have silencing activity for neural transcripts overlapping the repressive activity on neural genes of REST. We analyze properties of associated microRNA binding sites and contrast the outcome to the background. We found that the selected subset presents significant differences respect to the background: (i) lower GC-content in the vicinity of the predicted miRNA binding site, (ii) more target genes with multiple identical microRNA binding sites and (iii) a higher density of predicted microRNA binding sites close to the 3’ terminal end of the 3’-UTR. These results suggest that network selection of miRNA-mRNA pairs could provide useful features to improve microRNA target prediction.
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Zhang, Jiawei, Dandan Li, Rui Zhang, Rongxue Peng, and Jinming Li. "Delivery of microRNA-21-sponge and pre-microRNA-122 by MS2 virus-like particles to therapeutically target hepatocellular carcinoma cells." Experimental Biology and Medicine 246, no. 23 (October 13, 2021): 2463–72. http://dx.doi.org/10.1177/15353702211035689.
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MicroRNAs are related to the development of hepatocellular carcinoma and can serve as potential therapeutic targets. Therapeutic strategies increasing tumor-suppressive microRNAs and reducing oncogenic microRNAs have been developed. Herein, the effects of simultaneously altering two microRNAs using MS2 virus-like particles were studied. The sequences of microRNA-21-sponge and pre-microRNA-122 were connected and cloned into a virus-like particle expression vector. Virus-like particles containing microRNA-21-sponge and pre-microRNA-122 sequences were prepared and crosslinked with a cell-specific peptide targeting hepatocellular carcinoma cells. Delivery effects were studied using RT-qPCR and functional assays to investigate the level of target mRNAs, cell toxicity, and the effects of proliferation, invasion, and migration. Virus-like particles delivered miR-21-sponge into cells, with the Ct value reaching 10 at most. The linked pre-miR-122 was processed into mature miR-122. The mRNA targets of miR-21 were derepressed as predicted and upregulated 1.2–2.8-fold, and the expression of proteins was elevated correspondingly. Proliferation, migration, and invasion of HCC cells were inhibited by miR-21-sponge. Simultaneous delivery of miR-21-sponge and miR-122 further decreased proliferation, migration, and invasion by up to 34%, 63%, and 65%, respectively. And the combination promoted the apoptosis of HCC cells. In conclusion, delivering miR-21-sponge and miR-122 using virus-like particles modified by cell-specific peptides is an effective and convenient strategy to correct microRNA dysregulation in hepatocellular carcinoma cells and is a promising therapeutic strategy for hepatocellular carcinoma.
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Gareev, I. F., and O. A. Beylerli. "A STUDY OF THE ROLE OF MICRORNA IN PITUITARY ADENOMA." Advances in molecular oncology 5, no. 2 (July 17, 2018): 8–15. http://dx.doi.org/10.17650/2313-805x-2018-5-2-8-15.
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MicroRNAs are a new class of small non-coding RNAs, a length of 18–22 nucleotides that play a decisive role as posttranscriptional regulators of gene expression. Due to the large number of genes, regulated microRNAs, microRNAs are involved in many cellular processes. The study of the impairment of the expression of the target genes of microRNA, often associated with changes in important biological characteristics, provides a significant understanding of the role of microRNAs in oncogenesis. New evidence suggests that aberrant microRNA expression or dysregulation of endogenous microRNAs affects the onset and development of tumors, including adenomas of the pituitary gland. In this review, the significance of some microRNAs in the pathology of the pituitary adenoma will be assessed, as well as data on the study of microRNAs as therapeutic targets and new biomarkers.
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Kim, Hak Kyun, Yong Sun Lee, Umasundari Sivaprasad, Ankit Malhotra, and Anindya Dutta. "Muscle-specific microRNA miR-206 promotes muscle differentiation." Journal of Cell Biology 174, no. 5 (August 21, 2006): 677–87. http://dx.doi.org/10.1083/jcb.200603008.
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Three muscle-specific microRNAs, miR-206, -1, and -133, are induced during differentiation of C2C12 myoblasts in vitro. Transfection of miR-206 promotes differentiation despite the presence of serum, whereas inhibition of the microRNA by antisense oligonucleotide inhibits cell cycle withdrawal and differentiation, which are normally induced by serum deprivation. Among the many mRNAs that are down-regulated by miR-206, the p180 subunit of DNA polymerase α and three other genes are shown to be direct targets. Down-regulation of the polymerase inhibits DNA synthesis, an important component of the differentiation program. The direct targets are decreased by mRNA cleavage that is dependent on predicted microRNA target sites. Unlike small interfering RNA–directed cleavage, however, the 5′ ends of the cleavage fragments are distributed and not confined to the target sites, suggesting involvement of exonucleases in the degradation process. In addition, inhibitors of myogenic transcription factors, Id1-3 and MyoR, are decreased upon miR-206 introduction, suggesting the presence of additional mechanisms by which microRNAs enforce the differentiation program.
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Dahiya, Neetu, and Patrice J. Morin. "MicroRNAs in ovarian carcinomas." Endocrine-Related Cancer 17, no. 1 (March 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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Michaud, Pascale, Vivek Nilesh Shah, Pauline Adjibade, Francois Houle, Miguel Quévillon Huberdeau, Rachel Rioux, Camille Lavoie-Ouellet, Weifeng Gu, Rachid Mazroui, and Martin J. Simard. "The RabGAP TBC-11 controls Argonaute localization for proper microRNA function in C. elegans." PLOS Genetics 17, no. 4 (April 7, 2021): e1009511. http://dx.doi.org/10.1371/journal.pgen.1009511.
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Once loaded onto Argonaute proteins, microRNAs form a silencing complex called miRISC that targets mostly the 3’UTR of mRNAs to silence their translation. How microRNAs are transported to and from their target mRNA remains poorly characterized. While some reports linked intracellular trafficking to microRNA activity, it is still unclear how these pathways coordinate for proper microRNA-mediated gene silencing and turnover. Through a forward genetic screen usingCaenorhabditis elegans, we identified the RabGAPtbc-11as an important factor for the microRNA pathway. We show that TBC-11 acts mainly through the small GTPase RAB-6 and that its regulation is required for microRNA function. The absence of functional TBC-11 increases the pool of microRNA-unloaded Argonaute ALG-1 that is likely associated to endomembranes. Furthermore, in this condition, this pool of Argonaute accumulates in a perinuclear region and forms a high molecular weight complex. Altogether, our data suggest that the alteration of TBC-11 generates a fraction of ALG-1 that cannot bind to target mRNAs, leading to defective gene repression. Our results establish the importance of intracellular trafficking for microRNA function and demonstrate the involvement of a small GTPase and its GAP in proper Argonaute localizationin vivo.
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Chen, Lei, Yu Sun, Jinbo Li, and Yan Zhang. "A photoactivatable microRNA probe for identification of microRNA targets and light-controlled suppression of microRNA target expression." Chemical Communications 56, no. 4 (2020): 627–30. http://dx.doi.org/10.1039/c9cc08277h.
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Kelly, Elizabeth J., Rebecca Nace, Glen N. Barber, and Stephen J. Russell. "Attenuation of Vesicular Stomatitis Virus Encephalitis through MicroRNA Targeting." Journal of Virology 84, no. 3 (November 11, 2009): 1550–62. http://dx.doi.org/10.1128/jvi.01788-09.
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ABSTRACT Vesicular stomatitis virus (VSV) has long been regarded as a promising recombinant vaccine platform and oncolytic agent but has not yet been tested in humans because it causes encephalomyelitis in rodents and primates. Recent studies have shown that specific tropisms of several viruses could be eliminated by engineering microRNA target sequences into their genomes, thereby inhibiting spread in tissues expressing cognate microRNAs. We therefore sought to determine whether microRNA targets could be engineered into VSV to ameliorate its neuropathogenicity. Using a panel of recombinant VSVs incorporating microRNA target sequences corresponding to neuron-specific or control microRNAs (in forward and reverse orientations), we tested viral replication kinetics in cell lines treated with microRNA mimics, neurotoxicity after direct intracerebral inoculation in mice, and antitumor efficacy. Compared to picornaviruses and adenoviruses, the engineered VSVs were relatively resistant to microRNA-mediated inhibition, but neurotoxicity could nevertheless be ameliorated significantly using this approach, without compromise to antitumor efficacy. Neurotoxicity was most profoundly reduced in a virus carrying four tandem copies of a neuronal mir125 target sequence inserted in the 3′-untranslated region of the viral polymerase (L) gene.
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Lopez, Mary S., Robert J. Dempsey, and Raghu Vemuganti. "Resveratrol preconditioning induces cerebral ischemic tolerance but has minimal effect on cerebral microRNA profiles." Journal of Cerebral Blood Flow & Metabolism 36, no. 9 (July 21, 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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Yuan, Yao, Siddha Kasar, Chingiz Underbayev, Sindhuri Prakash, and Elizabeth Raveche. "MicroRNAs in Acute Myeloid Leukemia and Other Blood Disorders." Leukemia Research and Treatment 2012 (June 17, 2012): 1–11. http://dx.doi.org/10.1155/2012/603830.
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Common blood disorders include hematopoietic cell malignancies or leukemias and plasma cell dyscrasia, all of which have associated microRNA abnormalities. In this paper, we discuss several leukemias including acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) and identify altered microRNAs and their targets. Immune disorders with altered blood levels of antibodies include autoimmune disorders, such as systemic lupus erythematosus (SLE) with associated anti-self-autoantibodies and immunoglobulin A nephropathy (IgAN) also have related microRNA abnormalities. The alterations in microRNAs may serve as therapeutic targets in these blood disorders.
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Phuong, Ho Thi Bich, Vien Ngoc Thach, Luong Hoang Ngan, and Le Thi Truc Linh. "Using Bioinformatics to predict potential targets of Microrna-144 in osteoarthritis." ENGINEERING AND TECHNOLOGY 8, no. 1 (August 17, 2020): 43–52. http://dx.doi.org/10.46223/hcmcoujs.tech.en.8.1.335.2018.
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MicroRNAs are short endogenous non-coding RNA molecules, typically 19-25 nucleotides in length, which negatively regulate gene expression through binding to 3’UTR of target mRNAs, leading to repression of protein translation or target mRNA degradation. MicroRNA-144 (miR-144) was found as an abnormal expression in various diseases, including osteoarthritis (OA). We have identified increased microRNA-144 expression in early phase and
end stage of OA. However, the molecular mechanism of this increase has not been yet to be determined yet. Using bioinformatics tools, we found more than 4,000 mRNAs that are predicted to be potential direct targets of miR-144,
including mRNAs involved in the critical signaling pathways in OA e.g. TGFβ/Smad2/3 and WNT/β-catenin. Results from this research provide information for future ex periments to validate miR-144 potential targets.
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John, Bino, Anton J. Enright, Alexei Aravin, Thomas Tuschl, Chris Sander, and Debora S. Marks. "Correction: Human MicroRNA Targets." PLoS Biology 3, no. 7 (July 12, 2005): e264. http://dx.doi.org/10.1371/journal.pbio.0030264.
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Thomas, Marshall, Judy Lieberman, and Ashish Lal. "Desperately seeking microRNA targets." Nature Structural & Molecular Biology 17, no. 10 (October 2010): 1169–74. http://dx.doi.org/10.1038/nsmb.1921.
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Swingler, T. E., Y. Wormstone, M. Lott, M. Barter, D. Young, and I. M. Clark. "MicroRNA-455 targets Sirt1." Osteoarthritis and Cartilage 23 (April 2015): A275—A276. http://dx.doi.org/10.1016/j.joca.2015.02.504.
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MAZIERE, P., and A. ENRIGHT. "Prediction of microRNA targets." Drug Discovery Today 12, no. 11-12 (June 2007): 452–58. http://dx.doi.org/10.1016/j.drudis.2007.04.002.
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Cai, Meng, Gopi K. Kolluru, and Asif Ahmed. "Small Molecule, Big Prospects: MicroRNA in Pregnancy and Its Complications." Journal of Pregnancy 2017 (2017): 1–15. http://dx.doi.org/10.1155/2017/6972732.
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MicroRNAs are small, noncoding RNA molecules that regulate target gene expression in the posttranscriptional level. Unlike siRNA, microRNAs are “fine-tuners” rather than “switches” in the regulation of gene expression; thus they play key roles in maintaining tissue homeostasis. The aberrant microRNA expression is implicated in the disease process. To date, numerous studies have demonstrated the regulatory roles of microRNAs in various pathophysiological conditions. In contrast, the study of microRNA in pregnancy and its associated complications, such as preeclampsia (PE), fetal growth restriction (FGR), and preterm labor, is a young field. Over the last decade, the knowledge of pregnancy-related microRNAs has increased and the molecular mechanisms by which microRNAs regulate pregnancy or its associated complications are emerging. In this review, we focus on the recent advances in the research of pregnancy-related microRNAs, especially their function in pregnancy-associated complications and the potential clinical applications. Here microRNAs that associate with pregnancy are classified as placenta-specific, placenta-associated, placenta-derived circulating, and uterine microRNA according to their localization and origin. MicroRNAs offer a great potential for developing diagnostic and therapeutic targets in pregnancy-related disorders.
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Kirby, Tyler J., R. Grace Walton, Brian Finlin, Beibei Zhu, Resat Unal, Neda Rasouli, Charlotte A. Peterson, and Philip A. Kern. "Integrative mRNA-microRNA analyses reveal novel interactions related to insulin sensitivity in human adipose tissue." Physiological Genomics 48, no. 2 (February 2016): 145–53. http://dx.doi.org/10.1152/physiolgenomics.00071.2015.
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Adipose tissue has profound effects on whole-body insulin sensitivity. However, the underlying biological processes are quite complex and likely multifactorial. For instance, the adipose transcriptome is posttranscriptionally modulated by microRNAs, but the relationship between microRNAs and insulin sensitivity in humans remains to be determined. To this end, we utilized an integrative mRNA-microRNA microarray approach to identify putative molecular interactions that regulate the transcriptome in subcutaneous adipose tissue of insulin-sensitive (IS) and insulin-resistant (IR) individuals. Using the NanoString nCounter Human v1 microRNA Expression Assay, we show that 17 microRNAs are differentially expressed in IR vs. IS. Of these, 16 microRNAs (94%) are downregulated in IR vs. IS, including miR-26b, miR-30b, and miR-145. Using Agilent Human Whole Genome arrays, we identified genes that were predicted targets of miR-26b, miR-30b, and miR-145 and were upregulated in IR subjects. This analysis produced ADAM22, MYO5A, LOX, and GM2A as predicted gene targets of these microRNAs. We then validated that miR-145 and miR-30b regulate these mRNAs in differentiated human adipose stem cells. We suggest that use of bioinformatic integration of mRNA and microRNA arrays yields verifiable mRNA-microRNA pairs that are associated with insulin resistance and can be validated in vitro.
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Bujko, Mateusz, Paulina Kober, Joanna Boresowicz, Natalia Rusetska, Natalia Zeber-Lubecka, Agnieszka Paziewska, Monika Pekul, et al. "Differential microRNA Expression in USP8-Mutated and Wild-Type Corticotroph Pituitary Tumors Reflect the Difference in Protein Ubiquitination Processes." Journal of Clinical Medicine 10, no. 3 (January 20, 2021): 375. http://dx.doi.org/10.3390/jcm10030375.
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Background: USP8 mutations are the most common driver changes in corticotroph pituitary tumors. They have direct effect on cells’ proteome through disturbance of ubiquitination process and also influence gene expression. The aim of this study was to compare microRNA profiles in USP8-mutated and wild-type tumors and determine the probable role of differential microRNA expression by integrative microRNA and mRNA analysis. Methods: Patients with Cushing’s disease (n = 28) and silent corticotroph tumors (n = 20) were included. USP8 mutations were identified with Sanger sequencing. MicroRNA and gene expression was determined with next-generation sequencing. Results: USP8-mutated patients with Cushing’s disease showed higher rate of clinical remission and trend towards lower tumor volume than wild-type patients. Comparison of microRNA profiles of USP8-mutated and wild-type tumors revealed 68 differentially expressed microRNAs. Their target genes were determined by in silico prediction and microRNA/mRNA correlation analysis. GeneSet Enrichment analysis of putative targets showed that the most significantly overrepresented genes are involved in protein ubiquitination-related processes. Only few microRNAs influence the expression of genes differentially expressed between USP8-mutated and wild-type tumors. Conclusions: Differences in microRNA expression in corticotropinomas stratified according to USP8 status reflect disturbed ubiquitination processes, but do not correspond to differences in gene expression between these tumors.
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Zhang, Wei, Kai Liao, and Dongning Liu. "MiRNA-12129 Suppresses Cell Proliferation and Block Cell Cycle Progression by Targeting SIRT1 in GASTRIC Cancer." Technology in Cancer Research & Treatment 19 (January 1, 2020): 153303382092814. http://dx.doi.org/10.1177/1533033820928144.
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Gastric cancer is the most commonly occurring cancer with a rapidly increasing incidence rate worldwide. The underlying molecular mechanisms of gastric cancer require further investigation. MicroRNAs exhibit tissue sensitivity as tumor biomarkers that play a role by promoting tumor growth as oncogenes or tumor suppressor genes. We evaluated the effects of microRNA-12129 on gastric cancer and identified the underlying mechanisms of microRNA-12129. Quantitative real-time polymerase chain reaction was conducted to determine the expression levels of microRNA-12129 and sirtuin 1 in vivo and in vitro, and Western blot analysis was performed to detect sirtuin 1 at the protein level in gastric cancer cell lines. Cell proliferation and cell cycle progression were detected by Cell Counting Kit-8 assay and flow cytometry analysis, respectively. The potential targets of microRNA-12129 were predicted by bioinformatics analysis. The targets of microRNA-12129 were confirmed by luciferase reporter assay and rescue assay. We found that microRNA-12129 was downregulated in gastric cancer tissues and gastric cancer cell lines and was significantly associated with the prognosis of patients with gastric cancer. In addition, microRNA-12129 overexpression suppressed tumor cell proliferation and blocked cell cycle progression. Bioinformatics analysis and luciferase reporter assay suggested that sirtuin 1 was a target of microRNA-12129, and sirtuin 1 expression was negatively related to microRNA-12129. Restoration of sirtuin 1 partly reduced the inhibition of cell proliferation and cell cycle progression induced by microRNA-144. Our results collectively suggested that microRNA-12129 suppressed cell proliferation and cell cycle progression in gastric cancer by targeting sirtuin 1. These findings indicated that manipulation of microRNA-12129 expression could help develop a novel therapeutic strategy for gastric cancer.
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Marta, Gustavo Nader, Bernardo Garicochea, André Lopes Carvalho, Juliana M. Real, and Luiz Paulo Kowalski. "MicroRNAs, cancer and ionizing radiation: Where are we?" Revista da Associação Médica Brasileira 61, no. 3 (June 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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Hitu, Liviu, Katalin Gabora, Eduard-Alexandru Bonci, Andra Piciu, Adriana-Cezara Hitu, Paul-Andrei Ștefan, and Doina Piciu. "MicroRNA in Papillary Thyroid Carcinoma: A Systematic Review from 2018 to June 2020." Cancers 12, no. 11 (October 25, 2020): 3118. http://dx.doi.org/10.3390/cancers12113118.
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The involvement of micro-ribonucleic acid (microRNAs) in metabolic pathways such as regulation, signal transduction, cell maintenance, and differentiation make them possible biomarkers and therapeutic targets. The purpose of this review is to summarize the information published in the last two and a half years about the involvement of microRNAs in papillary thyroid carcinoma (PTC). Another goal is to understand the perspective offered by the new findings. Main microRNA features such as origin, regulation, targeted genes, and metabolic pathways will be presented in this paper. We interrogated the PubMed database using several keywords: “microRNA” + “thyroid” + “papillary” + “carcinoma”. After applying search filters and inclusion criteria, a selection of 137 articles published between January 2018–June 2020 was made. Data regarding microRNA, metabolic pathways, gene/protein, and study utility were selected and included in the table and later discussed regarding the matter at hand. We found that most microRNAs regularly expressed in the normal thyroid gland are downregulated in PTC, indicating an important tumor-suppressor action by those microRNAs. Moreover, we showed that one gene can be targeted by several microRNAs and have nominally described these interactions. We have revealed which microRNAs can target several genes at once.
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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, and Craig L. Slingluff. "MicroRNAs induced in melanoma treated with combination targeted therapy of temsirolimus and bevacizumab." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 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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Smit, Kyra N., Jiang Chang, Kasper Derks, Jolanda Vaarwater, Tom Brands, Rob M. Verdijk, Erik A. C. Wiemer, et al. "Aberrant MicroRNA Expression and Its Implications for Uveal Melanoma Metastasis." Cancers 11, no. 6 (June 12, 2019): 815. http://dx.doi.org/10.3390/cancers11060815.
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Uveal melanoma (UM) is the most frequently found primary intra-ocular tumor in adults. It is a highly aggressive cancer that causes metastasis-related mortality in up to half of the patients. Many independent studies have reported somatic genetic changes associated with high metastatic risk, such as monosomy of chromosome 3 and mutations in BAP1. Still, the mechanisms that drive metastatic spread are largely unknown. This study aimed to elucidate the potential role of microRNAs in the metastasis of UM. Using a next-generation sequencing approach in 26 UM samples we identified thirteen differentially expressed microRNAs between high-risk UM and low/intermediate-risk UM, including the known oncomirs microRNA-17-5p, microRNA-21-5p, and miR-151a-3p. Integration of the differentially expressed microRNAs with expression data of predicted target genes revealed 106 genes likely to be affected by aberrant microRNA expression. These genes were involved in pathways such as cell cycle regulation, EGF signaling and EIF2 signaling. Our findings demonstrate that aberrant microRNA expression in UM may affect the expression of genes in a variety of cancer-related pathways. This implies that some microRNAs can be responsible for UM metastasis and are promising potential targets for future treatment.
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Kulvait, Vojtech, Vit Pospisil, Karin Vargova, Marek Trneny, Pavel Klener, and Tomas Stopka. "Analysis of Mantle Cell Lymphoma Patients Reveals Novel Regulatory Circuits Involving MicroRNAs and Their Targets." Blood 118, no. 21 (November 18, 2011): 4624. http://dx.doi.org/10.1182/blood.v118.21.4624.4624.
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Abstract Abstract 4624 Mantle cell lymphoma (MCL) represents B-cell lymphoma derived from the mantle zone that surrounds normal germinal center follicles. Pathophysiology of this hardly curable disease involves t(11,14)(q13,q32) translocation which leads to upregulation of Cyclin D1(CCND1). Recently, microRNAs were demonstrated to significantly modify MCL pathogenesis (Jian-Jun Zhao et al. 2010) and therapy responsiveness (Jiang et al. 2010). In order to broaden our knowledge of regulatory pathways in MCL we searched for differentially expressed microRNAs and their differentially expressed mRNA targets between MCL samples and control samples. Samples consist of magnetically separated B cells derived from peripheral blood. We used 1) Microarray mRNA hybridization [Affymetrix Human Genome U133 Plus 2.0 Array, N(MCL)=5, N(control)=5] and 2) microRNA profiling [TaqMan® Array Human MicroRNA Card A v2.0 technology, N(MCL)=5, N(control)=5] followed by statistical analysis [limma (Smyth 2005)]. Differentially regulated targets of the deregulated microRNAs were selected from the databases involving both predicted (Betel et al. 2007) or confirmed (Hsu et al. 2010) target mRNAs. Among the most significant upregulated microRNAs (exceeding 10 fold) are miR-9, miR-124 and miR-183. We have found that upregulated miR-9 has confirmed downregulated target gene PRDM1 (PR domain zinc finger protein 1) which plays a role in B cell maturation (Turner et al. 1994) and may act as a tumor suppressor (Pasqualucci et al. 2006). Upregulation of miR-9 and downregulation of its targets was recently demonstrated in Burkitt lymphoma (Onnis A et al. 2010) and Hodgkin lymphoma (Nie K et al. 2008). Two additional upregulated microRNAs, miR-124 and miR-183, yet not associated with lymphomas, have downregulated target gene Integrin beta-1 (CD29) which regulates survival (Fukumori et al. 2003). Among most significant downregulated microRNAs is miR-101 (FC=-7). Downregulated microRNA miR-101 has known oncogene N-Myc (MYCN) as upregulated confirmed target and DNA (cytosine-5)-methyltransferase 3A (DNMT3A) as upregulated target. Overexpression of a well known hematopoietic oncogene MYCN and epigenetic repressor DNMT3A may represent additional pathogenesis-related factors in MCL. Our data support importance of the candidate mechanisms involving microRNAs and their target programs in pathogenesis of MCL. They are currently extended on a larger patient cohort by analyzing expression and functional significance of the candidate microRNAs. (Grants: NT10310-3/2009, MPO FR-TI2/509, NPVII 2B06077, MSM 0021620806, LC 06044, SVV-2011-262507). Disclosures: No relevant conflicts of interest to declare.
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Ali, S., O. Espin-Garcia, A. Wong, P. Potla, C. Pastrello, M. Mcintyre, S. Lively, I. Jurisica, R. Gandhi, and M. Kapoor. "POS0230 THE miR-320 FAMILY IS UPREGULATED IN FAST-PROGRESSING RADIOGRAPHIC KNEE OSTEOARTHRITIS: DATA FROM THE OSTEOARTHRITIS INITIATIVE." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 351.1–352. http://dx.doi.org/10.1136/annrheumdis-2022-eular.2970.
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BackgroundThere is an outstanding need for prognostic biomarkers to reliably detect fast-progressing knee osteoarthritis (OA) such that preventative interventions can be targeted to this patient population. MicroRNA-sequencing is an unbiased approach for comprehensive profiling of circulating microRNAs in liquid biopsies to discover novel biomarkers of disease. As negative regulators of gene expression, microRNAs hold potential not only as biomarkers, but also as mechanistic drivers of knee OA.ObjectivesTo apply microRNA-sequencing to identify unique circulating microRNAs as potential biomarkers that distinguish fast-progressing radiographic knee OA from both slow- and non-progressing radiographic knee OA.MethodsLeveraging the Osteoarthritis Initiative (OAI) longitudinal cohort, we applied our customized microRNA-sequencing pipeline [1] to blood plasma samples collected at both baseline and 4-year follow-up from 106 participants. The disease trajectory for each participant was constructed by plotting their Kellgren-Lawrence (KL) grades over an 8-year follow-up period. Based on these trajectories, we defined fast-progression as an increase from KL 0/1 at baseline to KL 3/4 by 4-year follow-up, slow-progression as an increase from KL 0/1 at baseline to KL 2/3/4 by 8-year follow-up, and non-progression as no increase from KL0/1 at baseline throughout the 8-year follow-up. Following differential expression analysis, we assessed predictive performance and identified putative gene targets for prioritized microRNAs.ResultsComparing fast-progressors to both slow-progressors and non-progressors, we identified differentially expressed microRNAs within timepoints (i.e., 48 microRNAs at baseline and 2 microRNAs at 4-year follow-up) and across timepoints. Among these microRNAs were four members of the miR-320 family, with miR-320d showing an increase in fast-progressors at both timepoints, compared to both slow- and non-progressors. The predictive models we constructed included miR-320 members and had good accuracy (area under the receiver operating characteristic curves ranging from 82.6 to 91.9) in distinguishing fast-progressors. Putative gene targets of the miR-320 family included members of the 14-3-3 gene family (Table 1), including YWHAE, whose downregulation in OA cartilage was reported to promote deterioration [2].Table 1.Predicted gene targets of the miR-320 family include members of the 14-3-3 gene family.14-3-3 gene family memberhsa-miR-320bhsa-miR-320chsa-miR-320dhsa-miR-320eSFNMMMLYWHABMMMMYWHAEVVVHYWHAGVVVMYWHAHVVVMYWHAQVVVMYWHAZVVVMAll mirDIP results with bold text indicating the prediction was among the top 1% for that microRNA/gene target pair. Letters denote the mirDIP score class with V=very high, H=high, M=medium, and L=low.ConclusionThis microRNA-sequencing study is the first of its kind, profiling circulating microRNAs at two timepoints in 106 participants with data-driven construction of knee OA trajectories. We identify the miR-320 family of microRNAs to be associated with fast-progressing radiographic knee OA over time. While our data suggest this microRNA family could have applications as prognostic biomarkers for knee OA, and could be regulating gene targets to impact OA severity, validation of these findings in independent longitudinal cohorts is required.References[1]Potla P, Ali SA, Kapoor M. A bioinformatics approach to microRNA-sequencing analysis. Osteoarthritis and Cartilage Open. 2021;3(1):100131. doi: https://doi.org/10.1016/j.ocarto.2020.100131.[2]Fu W, Hettinghouse A, Chen Y, Hu W, Ding X, Chen M, Ding Y, Mundra J, Song W, Liu R, Yi YS, Attur M, Samuels J, Strauss E, Leucht P, Schwarzkopf R, Liu CJ. 14-3-3 epsilon is an intracellular component of TNFR2 receptor complex and its activation protects against osteoarthritis. Ann Rheum Dis. 2021 Dec;80(12):1615-1627. doi: 10.1136/annrheumdis-2021-220000.Disclosure of InterestsNone declared
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Zhang, Hanyu, Mingxing Li, Parham Jabbarzadeh Kaboli, Huijiao Ji, Fukuan Du, Xu Wu, Yueshui Zhao, et al. "Identification of cluster of differentiation molecule-associated microRNAs as potential therapeutic targets for gastrointestinal cancer immunotherapy." International Journal of Biological Markers 36, no. 2 (March 31, 2021): 22–32. http://dx.doi.org/10.1177/17246008211005473.
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Background: Cluster of differentiation molecules are markers of immune cells that have been identified as a potential immunotherapeutic target for cancer treatment. MicroRNAs are small non-coding RNAs that act as tumor suppressors or oncogenes whose importance in diagnosis, prognosis, and treatment of gastric and colorectal cancers has been widely reported. However, their association with cluster of differentiation molecules in gastrointestinal cancers has not been well studied. Therefore, our study aimed to analyze the relationship between microRNAs and cluster of differentiation molecules in gastrointestinal cancers, and to identify cluster of differentiation molecule-associated microRNAs as prognostic biomarkers for gastrointestinal cancer patients. Methods: Targetscan, Starbase, DIANA microT, and miRDB were used to investigate microRNA profiles that might be correlated with cluster of differentiation molecules in gastrointestinal cancers. Moreover, The Cancer Genome Atlas data analysis was used to investigate the association between cluster of differentiation molecules and microRNA expression in patients with gastric, colon, rectal, pancreatic, and esophageal cancers. The Kaplan–Meier plotter was used to identify the association between overall survival and cluster of differentiation molecule-associated microRNA expression in gastrointestinal cancer patients. Results: miR-200a, miR-559, and miR-1236 were negatively associated with CD86, CD81, and CD160, respectively, in almost all types of gastrointestinal cancers, which were further verified in the in vitro studies by transfecting microRNA mimics in gastric cancer, colon cancer, pancreatic, and esophageal cell lines. Conclusion: Our study showed that miR-200a, miR-1236, and miR-559 are identified as cluster of differentiation-associated microRNAs in gastrointestinal cancers, providing a novel perspective to identify new therapeutic targets for cancer immunotherapy in gastrointestinal cancer patients.
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Guan, Yinuo, Xianjing Song, Wei Sun, Yiran Wang, and Bin Liu. "Effect of Hypoxia-Induced MicroRNA-210 Expression on Cardiovascular Disease and the Underlying Mechanism." Oxidative Medicine and Cellular Longevity 2019 (May 21, 2019): 1–12. http://dx.doi.org/10.1155/2019/4727283.
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Cardiovascular diseases have high morbidity and mortality rates worldwide, and their treatment and prevention are challenging. MicroRNAs are a series of noncoding RNAs with highly conserved sequences and regulate gene expression by inhibiting mRNA transcription or degrading targeting proteins. MicroRNA-210 is significantly upregulated during hypoxia and plays a protective role by inhibiting apoptosis and regulating cell proliferation, differentiation, migration, mitochondrial metabolism, and angiogenesis in hypoxic cells. MicroRNA-210 expression is altered in cardiovascular diseases such as atherosclerosis, acute myocardial infarction, preeclampsia, aortic stenosis, and heart failure, and overexpression of microRNA-210 in some of these diseases exerts protective effects on target organs. Furthermore, chronically upregulated miR-210 potentially plays a marked pathogenic role in specific situations. This review primarily focuses on the upstream pathways, downstream targets, clinical progress in cardiovascular disease, and potential applications of microRNA-210.
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Fadaka, Adewale Oluwaseun, Ashwil Klein, and Ashley Pretorius. "In silico identification of microRNAs as candidate colorectal cancer biomarkers." Tumor Biology 41, no. 11 (November 2019): 101042831988372. http://dx.doi.org/10.1177/1010428319883721.
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The involvement of microRNA in cancers plays a significant role in their pathogenesis. Specific expressions of these non-coding RNAs also serve as biomarkers for early colorectal cancer diagnosis, but their laboratory/molecular identification is challenging and expensive. The aim of this study was to identify potential microRNAs for colorectal cancer diagnosis using in silico approach. Sequence similarity search was employed to obtain the candidate microRNA from the datasets, and three target prediction software were employed to determine their target genes. To determine the involvement of these microRNAs in colorectal cancer, the microRNA gene list obtained was used alongside with colorectal cancer expressed genes from gbCRC and CoReCG databases for gene intersection analysis. The involvement of these genes in the cancer subtype was further strengthened with the DAVID database. KEGG and Gene Ontology were used for the pathway and functional analysis, while STRING was employed for the interactions of protein network and further visualized by Cytoscape. The cBioPortal database was used to prioritize the target genes; prognostic and expression analysis were finally performed on the candidate microRNAs and the prioritized targets. This study, therefore, identified five candidate microRNAs, two hub genes (CTNNB1 and epidermal growth factor receptor), and seven significant target genes associated with colorectal cancer. The molecular validation studies are ongoing to ascertain the biological fitness of these findings.
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Fadaka, Adewale, Ashley Pretorius, and Ashwil Klein. "MicroRNA Assisted Gene Regulation in Colorectal Cancer." International Journal of Molecular Sciences 20, no. 19 (October 3, 2019): 4899. http://dx.doi.org/10.3390/ijms20194899.
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Colorectal cancer (CRC) is the second-leading cause of cancer death and a major public health problem. Nearly 80% CRC cases are diagnosed after the disease have metastasized and are often too advanced for treatment. Small non-coding RNA guides argonaute protein to their specific target for regulation as the sole of RNA induced silencing complex for gene silencing. These non-coding RNA for example microRNA, are thought to play a key role in affecting the efficiency of gene regulation in cancer, especially CRC. Understanding the mechanism at the molecular level could lead to improved diagnosis, treatment, and management decisions for CRC. The study aimed to predict the molecular mechanism of gene regulation based microRNA-mRNA duplex as a lead in the silencing mechanism. Five candidate microRNAs were identified through the in silico approach. The MicroRNA target prediction and subsequent correlation, and prioritization were performed using miRTarBase, gbCRC and CoReCG, and DAVID databases respectively. Protein selection and preparation were carried out using PDB and Schrödinger suits. The molecular docking analysis was performed using PATCHDOCK webserver and visualized by discovery studio visualizer. The results of the study reveal that the candidate microRNAs have strong binding affinity towards their targets suggesting a crucial factor in the silencing mechanism. Furthermore, the molecular docking of the receptor to both the microRNA and microRNA-mRNA duplex were analyzed computationally to understand their interaction at the molecular level. Conclusively, the study provides an explanation for understanding the microRNAs-based gene regulation (silencing mechanism) in CRC.
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Poluliakh, O. E., E. I. Kalinovskaya, and A. A. Basalai. "Regulatory and therapeutic potential for obesity." Proceedings of the National Academy of Sciences of Belarus, Medical series 15, no. 4 (January 14, 2019): 483–92. http://dx.doi.org/10.29235/1814-6023-2018-15-4-483-492.
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A literature review about the role of microrna in biological processes associated with .obesity was completed. Modern ideas about micrornas, their biogenesis and their role in the formation of adipose tissue, glucose and lipid metabolism were described. The possibilities of using microRNA as new biomarkers and therapeutic targets for development of anti-obesity drugs were considered.
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Downing, Shawna, Fan Zhang, Zijing Chen, and Emmanuel S. Tzanakakis. "MicroRNA-7 directly targets Reg1 in pancreatic cells." American Journal of Physiology-Cell Physiology 317, no. 2 (August 1, 2019): C366—C374. http://dx.doi.org/10.1152/ajpcell.00013.2019.
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Regenerating islet-derived (Reg) proteins, which were first discovered in the pancreas, are associated with increased proliferation, prevention of apoptosis, and enhanced differentiation in normal and disease states, but very little is known about the regulation of their expression. We hypothesized that Reg expression is influenced by microRNAs. Bioinformatic analysis predicted Reg1 to be a target of microRNA-7 (miR-7), which influences pancreatic β-cell function. To this end, we investigated the effects of miR-7 on Reg1 expression in pancreatic acinar and islet β-cells. High levels of Reg1 were noted by immunostaining and Western blotting in acinar cells in contrast to islet cells. A reciprocal expression pattern was observed for miR-7. Overexpression of miR-7 resulted in Reg1 mRNA suppression and reduction of secreted Reg1 protein. Conversely, miR-7 knockdown led to increases in Reg1. Targeting of Reg1 by miR-7 was confirmed via luciferase activity assays. In contrast, miR-7 did not directly repress the human ortholog of Reg1 REG1A as well as REG1B indicating species differences in the regulation of Reg expression. This is the first account of microRNA modulation of any Reg member warranting studies to fill gaps in our knowledge of Reg protein biology, particularly in disease contexts.
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Islam, Md Tariqul, Ahlan Sabah Ferdous, Rifat Ara Najnin, Suprovath Kumar Sarker, and Haseena Khan. "High-Throughput Sequencing Reveals Diverse Sets of Conserved, Nonconserved, and Species-Specific miRNAs in Jute." International Journal of Genomics 2015 (2015): 1–14. http://dx.doi.org/10.1155/2015/125048.
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MicroRNAs play a pivotal role in regulating a broad range of biological processes, acting by cleaving mRNAs or by translational repression. A group of plant microRNAs are evolutionarily conserved; however, others are expressed in a species-specific manner. Jute is an agroeconomically important fibre crop; nonetheless, no practical information is available for microRNAs in jute to date. In this study, Illumina sequencing revealed a total of 227 known microRNAs and 17 potential novel microRNA candidates in jute, of which 164 belong to 23 conserved families and the remaining 63 belong to 58 nonconserved families. Among a total of 81 identified microRNA families, 116 potential target genes were predicted for 39 families and 11 targets were predicted for 4 among the 17 identified novel microRNAs. For understanding better the functions of microRNAs, target genes were analyzed by Gene Ontology and their pathways illustrated by KEGG pathway analyses. The presence of microRNAs identified in jute was validated by stem-loop RT-PCR followed by end point PCR and qPCR for randomly selected 20 known and novel microRNAs. This study exhaustively identifies microRNAs and their target genes in jute which will ultimately pave the way for understanding their role in this crop and other crops.
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Muñoz-Alarcón, Andrés, Peter Guterstam, Cristian Romero, Mark A. Behlke, Kim A. Lennox, Jesper Wengel, Samir EL Andaloussi, and Ülo Langel. "Modulating Anti-MicroRNA-21 Activity and Specificity Using Oligonucleotide Derivatives and Length Optimization." ISRN Pharmaceutics 2012 (February 7, 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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Zhu, Yujie, Yuxin Lin, Wenying Yan, Zhandong Sun, Zhi Jiang, Bairong Shen, Xiaoqian Jiang, and Jingjing Shi. "Novel Biomarker MicroRNAs for Subtyping of Acute Coronary Syndrome: A Bioinformatics Approach." BioMed Research International 2016 (2016): 1–11. http://dx.doi.org/10.1155/2016/4618323.
Full textAbstract:
Acute coronary syndrome (ACS) is a life-threatening disease that affects more than half a million people in United States. We currently lack molecular biomarkers to distinguish the unstable angina (UA) and acute myocardial infarction (AMI), which are the two subtypes of ACS. MicroRNAs play significant roles in biological processes and serve as good candidates for biomarkers. In this work, we collected microRNA datasets from the Gene Expression Omnibus database and identified specific microRNAs in different subtypes and universal microRNAs in all subtypes based on our novel network-based bioinformatics approach. These microRNAs were studied for ACS association by pathway enrichment analysis of their target genes. AMI and UA were associated with 27 and 26 microRNAs, respectively, nine of them were detected for both AMI and UA, and five from each subtype had been reported previously. The remaining 22 and 21 microRNAs are novel microRNA biomarkers for AMI and UA, respectively. The findings are then supported by pathway enrichment analysis of the targets of these microRNAs. These novel microRNAs deserve further validation and will be helpful for personalized ACS diagnosis.
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Zou, Yan-Fang, and Wen Zhang. "Role of microRNA in the detection, progression, and intervention of acute kidney injury." Experimental Biology and Medicine 243, no. 2 (December 21, 2017): 129–36. http://dx.doi.org/10.1177/1535370217749472.
Full textAbstract:
Acute kidney injury, characterized by sharply decreased renal function, is a common and important complication in hospitalized patients. The pathological mechanism of acute kidney injury is mainly related to immune activation and inflammation. Given the high morbidity and mortality rates of hospitalized patients with acute kidney injury, the identification of biomarkers useful for assessing risk, making an early diagnosis, evaluating the prognosis, and classifying the injury severity is urgently needed. Furthermore, investigation into the development of acute kidney injury and potential therapeutic targets is required. While microRNA was first discovered in Caenorhabditis elegans, Gary Ruvkun’s laboratory identified the first microRNA target gene. Together, these two important findings confirmed the existence of a novel post-transcriptional gene regulatory mechanism. Considering that serum creatinine tests often fail in the early detection of AKI, testing for microRNAs as early diagnostic biomarkers has shown great potential. Numerous studies have identified microRNAs that can serve as biomarkers for the detection of acute kidney injury. In addition, as microRNAs can control the expression of multiple proteins through hundreds or thousands of targets influencing multiple signaling pathways, the number of studies on the functions of microRNAs in AKI progression is increasing. Here, we mainly focus on research into microRNAs as biomarkers and explorations of their functions in acute kidney injury. Impact statement Firstly, we have discussed the potential advantages and limitations of miRNA as biomarkers. Secondly, we have summarized the role of miRNA in the progress of AKI. Finally, we have made a vision of miRNA’s potential and advantages as therapeutic target intervention AKI.