Journal articles on the topic 'NcRNAs, lncRNAs, miRNA, immunity'
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1
Schaefer, Jeremy, and Trevor Schnupp. "Non-coding RNA regulation of immunity." Journal of Immunology 200, no. 1_Supplement (May 1, 2018): 167.9. http://dx.doi.org/10.4049/jimmunol.200.supp.167.9.
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Abstract Non-coding RNAs (ncRNAs) comprise a diverse range of biologically functional RNA species that include long ncRNAs (lncRNA) and short ncRNAs such as piwi-interacting RNAs (piRNA) and microRNAs (miRNA). These ncRNAs are capable of regulating gene expression via distinct mechanisms depending on their structure---miRNAs bind specific messenger RNAs (mRNA) to block translation while lncRNAs tend to bind chromatin to modify chromatin states to interfere with gene expression. NcRNAs have been identified in numerous diseases as having altered expression. To further elucidate the role of ncRNAs in immunity, we conducted a screen of lncRNA expression in the interleukin-10 knockout mouse (IL-10−/−) model of intestinal inflammation. This screen identified several candidate lncRNAs with dysregulated expression. Importantly, our data demonstrate that Malat1 and Hoxa11as expression was significantly decreased in mice with severe intestinal pathology. These results suggest that an association exists between these lncRNAs and the progression of disease in the IL-10−/− mouse model of colitis.
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Guidi, Riccardo, Christopher J. Wedeles, and Mark S. Wilson. "ncRNAs in Type-2 Immunity." Non-Coding RNA 6, no. 1 (March 6, 2020): 10. http://dx.doi.org/10.3390/ncrna6010010.
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Immunological diseases, including asthma, autoimmunity and immunodeficiencies, affect a growing percentage of the population with significant unmet medical needs. As we slowly untangle and better appreciate these complex genetic and environment-influenced diseases, new therapeutically targetable pathways are emerging. Non-coding RNA species, which regulate epigenetic, transcriptional and translational responses are critical regulators of immune cell development, differentiation and effector function, and may represent one such new class of therapeutic targets. In this review we focus on type-2 immune responses, orchestrated by TH2 cell-derived cytokines, IL-4, IL-5 and IL-13, which stimulate a variety of immune and tissue responses- commonly referred to as type-2 immunity. Evolved to protect us from parasitic helminths, type-2 immune responses are observed in individuals with allergic diseases, including Asthma, atopic dermatitis and food allergy. A growing number of studies have identified the involvement of various RNA species, including microRNAs (miRNA) and long non-coding (lncRNA), in type-2 immune responses and in both clinical and pre-clinical disease settings. We highlight these recent findings, identify gaps in our understanding and provide a perspective on how our current understanding can be harnessed for novel treat opportunities to treat type-2 immune-mediated diseases.
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Nadarajah, Kalaivani K., and Nur Sabrina Natasha Abdul Rahman. "The Role of Non-Coding RNA in Rice Immunity." Agronomy 12, no. 1 (December 24, 2021): 39. http://dx.doi.org/10.3390/agronomy12010039.
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Disease has been a major concern in the rice-growing sector, resulting in significant losses and compromised food security. To combat disease, plants have devised various defense strategies. Initial works in understanding plant–pathogen interactions were focused on discovering resistance and pathogenicity genes, as well as analyzing the functions of these genes in the host defense. Later, researchers discovered that regulatory elements, such as transcription factors, were essential players in modulating plant defenses. As the depth of research and knowledge in this field increased, non-coding RNA (ncRNA) were discovered to play key functions in plant immunity. In this review, we explore the contribution and interaction of microRNAs (miRNAs), long ncRNAs (lncRNAs), and small interfering RNAs (siRNAs) in controlling the rice immune response. The role and the interaction between ncRNAs and their targets have been discussed in detail. We believe that this information will be beneficial in disease resistance breeding of rice.
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Papaioannou, Eleftheria, María del Pilar González-Molina, Ana M. Prieto-Muñoz, Laura Gámez-Reche, and Alicia González-Martín. "Regulation of Adaptive Tumor Immunity by Non-Coding RNAs." Cancers 13, no. 22 (November 12, 2021): 5651. http://dx.doi.org/10.3390/cancers13225651.
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Cancer immunology research has mainly focused on the role of protein-coding genes in regulating immune responses to tumors. However, despite more than 70% of the human genome is transcribed, less than 2% encodes proteins. Many non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have been identified as critical regulators of immune cell development and function, suggesting that they might play important roles in orchestrating immune responses against tumors. In this review, we summarize the scientific advances on the role of ncRNAs in regulating adaptive tumor immunity, and discuss their potential therapeutic value in the context of cancer immunotherapy.
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Ma, Minjuan, Rui Duan, Hong Zhong, Tingming Liang, and Li Guo. "The Crosstalk between Fat Homeostasis and Liver Regional Immunity in NAFLD." Journal of Immunology Research 2019 (January 3, 2019): 1–10. http://dx.doi.org/10.1155/2019/3954890.
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The liver is well known as the center of glucose and lipid metabolism in the human body. It also functions as an immune organ. Previous studies have suggested that liver nonparenchymal cells are crucial in the progression of NAFLD. In recent years, NAFLD’s threat to human health has been becoming a global issue. And by far, there is no effective treatment for NAFLD. Liver nonparenchymal cells are stimulated by lipid antigens, adipokines, or other factors, and secreted immune factors can alter the expression of key proteins such as SREBP-1c, ChREBP, and PPARγ to regulate lipid metabolism, thus affecting the pathological process of NAFLD. Interestingly, some ncRNAs (including miRNAs and lncRNAs) participate in the pathological process of NAFLD by changing body fat homeostasis. And even some ncRNAs could regulate the activity of HSCs, thereby affecting the progression of inflammation and fibrosis in the course of NAFLD. In conclusion, immunotherapy could be an effective way to treat NAFLD.
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Feng, Qingqing, Hongli Zhang, Denglin Yao, Wei-Dong Chen, and Yan-Dong Wang. "Emerging Role of Non-Coding RNAs in Esophageal Squamous Cell Carcinoma." International Journal of Molecular Sciences 21, no. 1 (December 30, 2019): 258. http://dx.doi.org/10.3390/ijms21010258.
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Esophageal squamous cell carcinoma (ESCC) is a highly prevalent tumor and is associated with ethnicity, genetics, and dietary intake. Non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs) have been reported as functional regulatory molecules involved in the development of many human cancers, including ESCC. Recently, several ncRNAs have been detected as oncogenes or tumor suppressors in ESCC progression. These ncRNAs influence the expression of specific genes or their associated signaling pathways. Moreover, interactions of ncRNAs are evident in ESCC, as miRNAs regulate the expression of lncRNAs, and further, lncRNAs and circRNAs function as miRNA sponges to compete with the endogenous RNAs. Here, we discuss and summarize the findings of recent investigations into the role of ncRNAs (miRNAs, lncRNAs, and circRNAs) in the development and progression of ESCC and how their interactions regulate ESCC development.
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Roberts, Thomas C., and Matthew J. A. Wood. "Therapeutic targeting of non-coding RNAs." Essays in Biochemistry 54 (April 30, 2013): 127–45. http://dx.doi.org/10.1042/bse0540127.
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ncRNAs (non-coding RNAs) are implicated in a wide variety of cellular processes, including the regulation of gene expression. In the present chapter we consider two classes of ncRNA: miRNAs (microRNAs) which are post-transcriptional regulators of gene expression and lncRNAs (long ncRNAs) which mediate interactions between epigenetic remodelling complexes and chromatin. Mutation and misexpression of ncRNAs have been implicated in many disease conditions and, as such, pharmacological modulation of ncRNAs is a promising therapeutic approach. miRNA activity can be antagonized with antisense oligonucleotides which sequester or degrade mature miRNAs, and expressed miRNA sponges which compete with target transcripts for miRNA binding. Conversely, synthetic or expressed miRNA mimics can be used to treat a deficiency in miRNA expression. Similarly, conventional antisense technologies can be used to silence lncRNAs. Targeting promoter-associated RNAs with siRNAs (small interfering RNAs) results in recruitment of chromatin-modifying activities and induces transcriptional gene silencing. Alternatively, targeting natural antisense transcripts with siRNAs or antisense oligonucleotides can abrogate endogenous epigenetic silencing leading to transcriptional gene activation. The ability to modulate gene expression at the epigenetic level presents exciting new opportunities for the treatment of human disease.
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Bai, Xiang-feng, Rui-ze Niu, Jia Liu, Xu-dong Pan, Feng Wang, Wei Yang, Lu-qiao Wang, and Li-zhong Sun. "Roles of noncoding RNAs in the initiation and progression of myocardial ischemia–reperfusion injury." Epigenomics 13, no. 9 (May 2021): 715–43. http://dx.doi.org/10.2217/epi-2020-0359.
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The morbidity and mortality of myocardial ischemia–reperfusion injury (MIRI) have increased in modern society. Noncoding RNAs (ncRNAs), including lncRNAs, circRNAs, piRNAs and miRNAs, have been reported in a variety of studies to be involved in pathological initiation and developments of MIRI. Hence this review focuses on the current research regarding these ncRNAs in MIRI. We comprehensively introduce the important features of lncRNAs, circRNAs, piRNA and miRNAs and then summarize the published studies of ncRNAs in MIRI. A clarification of lncRNA–miRNA–mRNA, lncRNA–transcription factor–mRNA and circRNA–miRNA–mRNA axes in MIRI follows, to further elucidate the crucial roles of ncRNAs in MIRI. Bioinformatics analysis has revealed the biological correlation of mRNAs with MIRI. We provide a comprehensive perspective for the roles of these ncRNAs and their related networks in MIRI, providing a theoretical basis for preclinical and clinical studies on ncRNA-based gene therapy for MIRI treatment.
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Bhogireddy, Sailaja, Satendra K. Mangrauthia, Rakesh Kumar, Arun K. Pandey, Sadhana Singh, Ankit Jain, Hikmet Budak, Rajeev K. Varshney, and Himabindu Kudapa. "Regulatory non-coding RNAs: a new frontier in regulation of plant biology." Functional & Integrative Genomics 21, no. 3-4 (May 20, 2021): 313–30. http://dx.doi.org/10.1007/s10142-021-00787-8.
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AbstractBeyond the most crucial roles of RNA molecules as a messenger, ribosomal, and transfer RNAs, the regulatory role of many non-coding RNAs (ncRNAs) in plant biology has been recognized. ncRNAs act as riboregulators by recognizing specific nucleic acid targets through homologous sequence interactions to regulate plant growth, development, and stress responses. Regulatory ncRNAs, ranging from small to long ncRNAs (lncRNAs), exert their control over a vast array of biological processes. Based on the mode of biogenesis and their function, ncRNAs evolved into different forms that include microRNAs (miRNAs), small interfering RNAs (siRNAs), miRNA variants (isomiRs), lncRNAs, circular RNAs (circRNAs), and derived ncRNAs. This article explains the different classes of ncRNAs and their role in plant development and stress responses. Furthermore, the applications of regulatory ncRNAs in crop improvement, targeting agriculturally important traits, have been discussed.
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DeOcesano-Pereira, Carlos, Raquel A. C. Machado, Ana Marisa Chudzinski-Tavassi, and Mari Cleide Sogayar. "Emerging Roles and Potential Applications of Non-Coding RNAs in Glioblastoma." International Journal of Molecular Sciences 21, no. 7 (April 9, 2020): 2611. http://dx.doi.org/10.3390/ijms21072611.
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Non-coding RNAs (ncRNAs) comprise a diversity of RNA species, which do not have the potential to encode proteins. Non-coding RNAs include two classes of RNAs, namely: short regulatory ncRNAs and long non-coding RNAs (lncRNAs). The short regulatory RNAs, containing up to 200 nucleotides, include small RNAs, such as microRNAs (miRNA), short interfering RNAs (siRNAs), piwi-interacting RNAs (piRNAs), and small nucleolar RNAs (snoRNAs). The lncRNAs include long antisense RNAs and long intergenic RNAs (lincRNAs). Non-coding RNAs have been implicated as master regulators of several biological processes, their expression being strictly regulated under physiological conditions. In recent years, particularly in the last decade, substantial effort has been made to investigate the function of ncRNAs in several human diseases, including cancer. Glioblastoma is the most common and aggressive type of brain cancer in adults, with deregulated expression of small and long ncRNAs having been implicated in onset, progression, invasiveness, and recurrence of this tumor. The aim of this review is to guide the reader through important aspects of miRNA and lncRNA biology, focusing on the molecular mechanism associated with the progression of this highly malignant cancer type.
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Gong, Chengwu, Xueliang Zhou, Songqing Lai, Lijun Wang, and Jichun Liu. "Long Noncoding RNA/Circular RNA-miRNA-mRNA Axes in Ischemia-Reperfusion Injury." BioMed Research International 2020 (November 25, 2020): 1–33. http://dx.doi.org/10.1155/2020/8838524.
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Ischemia-reperfusion injury (IRI) elicits tissue injury involved in a wide range of pathologies. Multiple studies have demonstrated that noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs), participate in the pathological development of IRI, and they may act as biomarkers, therapeutic targets, or prognostic indicators. Nonetheless, the specific molecular mechanisms of ncRNAs in IRI have not been completely elucidated. Regulatory networks among lncRNAs/circRNAs, miRNAs, and mRNAs have been the focus of attention in recent years. Studies on the underlying molecular mechanisms have contributed to the discovery of therapeutic targets or strategies in IRI. In this review, we comprehensively summarize the current research on the lncRNA/circRNA-miRNA-mRNA axes and highlight the important role of these axes in IRI.
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Fittipaldi, Simona, Virginia Veronica Visconti, Umberto Tarantino, Giuseppe Novelli, and Annalisa Botta. "Genetic variability in noncoding RNAs: involvement of miRNAs and long noncoding RNAs in osteoporosis pathogenesis." Epigenomics 12, no. 22 (November 2020): 2035–49. http://dx.doi.org/10.2217/epi-2020-0233.
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The pathogenesis of osteoporosis is multifactorial and is the consequence of genetic, hormonal and lifestyle factors. Epigenetics, including noncoding RNA (ncRNA) deregulation, represents a link between susceptibility to develop the disease and environmental influences. The majority of studies investigated the expression of ncRNAs in osteoporosis patients; however, very little information is available on their genetic variability. In this review, we focus on two classes of ncRNAs: miRNAs and long noncoding RNAs (lncRNAs). We summarize recent findings on how polymorphisms in miRNAs and lncRNAs can perturb the lncRNA/miRNA/mRNA axis and may be involved in osteoporosis clinical outcome. We also provide a general overview on databases and bioinformatic tools useful for associating miRNAs and lncRNAs variability with complex genetic diseases.
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Matjašič, Alenka, Mojca Tajnik, Emanuela Boštjančič, Mara Popović, Boštjan Matos, and Damjan Glavač. "Identifying Novel Glioma-Associated Noncoding RNAs by Their Expression Profiles." International Journal of Genomics 2017 (2017): 1–18. http://dx.doi.org/10.1155/2017/2312318.
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Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) play a significant role in cancer development as regulators of protein-coding genes. Their dysregulation was in some extent already associated with glioma, the most aggressive primary brain tumours in adults. The correct diagnosis and treatment selection due to high tumour heterogeneity might be difficult and inadequate, resulting in poor prognosis. Studies of expression patterns of noncoding RNAs (ncRNAs) could provide useful insight in glioma molecular development. We used the qPCR approach to screen and investigate the expression of lncRNAs that were previously deregulated in other cancer types. The study showed altered expression levels for numerous lncRNAs across histologically different glioma samples. Validation of few lncRNAs showed association of expression levels with histological subtype and/or malignancy grade. We also observed deregulated and subtype-distinctive expression for four lncRNA-associated miRNAs. Expression of few lncRNAs and miRNA was also associated with patients’ survival, showing potential prognostic value. Several ncRNAs, some already related to glioma and some, to the best of our knowledge, investigated for the first time, might be of greater importance in glioma molecular development and progression. Finding the subtype-specific lncRNA and/or miRNA expression patterns may contribute additional information for a more objective classification.
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Falcon, Tiago, Martiela Freitas, Ana Carolina Mello, Laura Coutinho, Mario R. Alvares-da-Silva, and Ursula Matte. "Analysis of the Cancer Genome Atlas Data Reveals Novel Putative ncRNAs Targets in Hepatocellular Carcinoma." BioMed Research International 2018 (June 26, 2018): 1–9. http://dx.doi.org/10.1155/2018/2864120.
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Hepatocellular carcinoma (HCC) is the prevalent type of primary liver malignancy. Different noncoding RNAs (ncRNAs) that negatively regulate gene expression, such as the microRNAs and the long ncRNAs (lncRNAs), have been associated with cell invasiveness and cell dissemination, tumor recurrence, and metastasis in HCC. To evaluate which regulatory ncRNAs might be good candidates to disrupt HCC proliferation pathways, we performed both unsupervised and supervised analyses of HCC expression data, comparing samples of solid tumor tissue (TP) and adjacent tissue (NT) of a set of patients, focusing on ncRNAs and searching for common mechanisms that may shed light in future therapeutic options. All analyses were performed using the R software. Differential expression (total RNA and miRNA) and enrichment analyses (Gene Ontology + Pathways) were performed using the package TCGABiolinks. As a result, we improved the set of lncRNAs that could be the target of future studies in HCC, highlighting the potential ofFAM170B-AS1andTTN-AS1.
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Pandey, Amitkumar, Saiprasad Ajgaonkar, Nikita Jadhav, Praful Saha, Pranay Gurav, Sangita Panda, Dilip Mehta, and Sujit Nair. "Current Insights into miRNA and lncRNA Dysregulation in Diabetes: Signal Transduction, Clinical Trials and Biomarker Discovery." Pharmaceuticals 15, no. 10 (October 14, 2022): 1269. http://dx.doi.org/10.3390/ph15101269.
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Diabetes is one of the most frequently occurring metabolic disorders, affecting almost one tenth of the global population. Despite advances in antihyperglycemic therapeutics, the management of diabetes is limited due to its complexity and associated comorbidities, including diabetic neuropathy, diabetic nephropathy and diabetic retinopathy. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are involved in the regulation of gene expression as well as various disease pathways in humans. Several ncRNAs are dysregulated in diabetes and are responsible for modulating the expression of various genes that contribute to the ‘symptom complex’ in diabetes. We review various miRNAs and lncRNAs implicated in diabetes and delineate ncRNA biological networks as well as key ncRNA targets in diabetes. Further, we discuss the spatial regulation of ncRNAs and their role(s) as prognostic markers in diabetes. We also shed light on the molecular mechanisms of signal transduction with diabetes-associated ncRNAs and ncRNA-mediated epigenetic events. Lastly, we summarize clinical trials on diabetes-associated ncRNAs and discuss the functional relevance of the dysregulated ncRNA interactome in diabetes. This knowledge will facilitate the identification of putative biomarkers for the therapeutic management of diabetes and its comorbidities. Taken together, the elucidation of the architecture of signature ncRNA regulatory networks in diabetes may enable the identification of novel biomarkers in the discovery pipeline for diabetes, which may lead to better management of this metabolic disorder.
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Hu, Weiguo, Guanghao Wang, Siwen Wang, Xiaojun Nie, Changyou Wang, Yajuan Wang, Hong Zhang, and Wanquan Ji. "Co-Regulation of Long Non-Coding RNAs with Allele-Specific Genes in Wheat Responding to Powdery Mildew Infection." Agronomy 10, no. 6 (June 24, 2020): 896. http://dx.doi.org/10.3390/agronomy10060896.
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Powdery mildew (caused by Blumeria graminis f. sp. tritici; Bgt) is an important fungal disease of wheat (Triticum aestivum) worldwide, and results in significant crop damage in epidemic years. Understanding resistance mechanisms could have undoubted benefits in controlling disease and minimizing crop losses. The recent explosion in genomic knowledge and the discovery of noncoding RNAs have led to the idea that long ncRNAs (lncRNAs) might be key regulators of protein-coding gene expression. However, in-depth functional analyses of lncRNAs in wheat remain limited. Here, we evaluated the possible role of lncRNAs in regulating functional genes in wheat responding to Bgt pathogen, using genome-wide transcriptome data and quantitative RT-PCR. Our results demonstrated that both long intron ncRNAs (linncRNA) and long intergenic ncRNAs (lincRNAs) play roles in regulating allele-specific genes, including transcription factors, both positively and negatively. The correlation of expression between lincRNAs and flanking functional genes increased as the spacing distance decreased. Co-expression of microRNAs, their target lncRNA and target functional genes showed that lincRNA interacted competitively with functional genes via miRNA regulation. These results will be beneficial for further dissecting molecular mechanisms of lncRNAs functions at the transcriptional and post-transcriptional levels in wheat.
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Lulli, Matteo, Cristina Napoli, Ida Landini, Enrico Mini, and Andrea Lapucci. "Role of Non-Coding RNAs in Colorectal Cancer: Focus on Long Non-Coding RNAs." International Journal of Molecular Sciences 23, no. 21 (November 3, 2022): 13431. http://dx.doi.org/10.3390/ijms232113431.
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Colorectal cancer is one of the most common causes of cancer-related deaths worldwide. Despite the advances in the knowledge of pathogenetic molecular mechanisms and the implementation of more effective drug treatments in recent years, the overall survival rate of patients remains unsatisfactory. The high death rate is mainly due to metastasis of cancer in about half of the cancer patients and the emergence of drug-resistant populations of cancer cells. Improved understanding of cancer molecular biology has highlighted the role of non-coding RNAs (ncRNAs) in colorectal cancer development and evolution. ncRNAs regulate gene expression through various mechanisms, including epigenetic modifications and interactions of long non-coding RNAs (lncRNAs) with both microRNAs (miRNAs) and proteins, and through the action of lncRNAs as miRNA precursors or pseudogenes. LncRNAs can also be detected in the blood and circulating ncRNAs have become a new source of non-invasive cancer biomarkers for the diagnosis and prognosis of colorectal cancer, as well as for predicting the response to drug therapy. In this review, we focus on the role of lncRNAs in colorectal cancer development, progression, and chemoresistance, and as possible therapeutic targets.
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Xiao, Dandan, Min Chen, Xiaoqian Yang, Hai Bao, Yuzhang Yang, and Yanwei Wang. "The Intersection of Non-Coding RNAs Contributes to Forest Trees’ Response to Abiotic Stress." International Journal of Molecular Sciences 23, no. 12 (June 7, 2022): 6365. http://dx.doi.org/10.3390/ijms23126365.
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Non-coding RNAs (ncRNAs) play essential roles in plants by modulating the expression of genes at the transcriptional or post-transcriptional level. In recent years, ncRNAs have been recognized as crucial regulators for growth and development in forest trees, and ncRNAs that respond to various abiotic stresses are now under intense study. In this review, we summarized recent advances in the understanding of abiotic stress-responsive microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in forest trees. Furthermore, we analyzed the intersection of miRNAs, and epigenetic modified ncRNAs of forest trees in response to abiotic stress. In particular, the abiotic stress-related lncRNA/circRNA–miRNA–mRNA regulatory network of forest trees was explored.
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Shi, Rou, Yingjian Chen, Yuanjun Liao, Rang Li, Chunwen Lin, Liangchang Xiu, Haibing Yu, and Yuanlin Ding. "Research Status of Differentially Expressed Noncoding RNAs in Type 2 Diabetes Patients." BioMed Research International 2020 (November 13, 2020): 1–18. http://dx.doi.org/10.1155/2020/3816056.
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Aims. Noncoding RNAs (ncRNAs) play an important role in the occurrence and development of type 2 diabetes mellitus (T2DM). This paper summarized the current evidences of the involvement microRNAs, long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in the differential expressions and their interaction with each other in T2DM. Methods. The differentially expressed miRNAs, lncRNAs, and circRNAs in the blood circulation (plasma, serum, whole blood, and peripheral blood mononuclear cells) of patients with T2DM were found in PubMed, GCBI, and other databases. The interactions between ncRNAs were predicted based on the MiRWalk and the DIANA Tools databases. The indirect and direct target genes of lncRNAs and circRNAs were predicted based on the starBase V2.0, DIANA Tools, and LncRNA-Target databases. Then, GO and KEGG analysis on all miRNA, lncRNA, and circRNA target genes was performed using the mirPath and Cluster Profile software package in R language. The lncRNA–miRNA and circRNA–miRNA interaction diagram was constructed with Cytoscape. The aim of this investigation was to construct a mechanism diagram of lncRNA involved in the regulation of target genes on insulin signaling pathways and AGE–RAGE signaling pathways of diabetic complications. Results. A total of 317 RNAs, 283 miRNAs, and 20 lncRNAs and circRNAs were found in the circulation of T2DM. Dysregulated microRNAs and lncRNAs were found to be involved in signals related to metabolic disturbances, insulin signaling, and AGE–RAGE signaling in T2DM. In addition, lncRNAs participate in the regulation of key genes in the insulin signaling and AGE–RAGE signaling pathways through microRNAs, which leads to insulin resistance and diabetic vascular complications. Conclusion. Noncoding RNAs participate in the occurrence and development of type 2 diabetes and lead to its vascular complications by regulating different signaling pathways.
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Chen, Yanxia, Dong Chen, Jing Wang, Yu Zhang, Ji Zhang, Bing Chen, Yaru Chen, Yi Zhang, and Cailing Ma. "Dysregulated LncRNAs Act as Competitive Endogenous RNAs and Are Associated With Cervical Cancer Development in UYGHUR Women." Technology in Cancer Research & Treatment 20 (January 1, 2021): 153303382198971. http://dx.doi.org/10.1177/1533033821989711.
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Cervical cancer is one of the most malignant tumors in women, particularly those in rural and remote areas. Its underlying molecular mechanisms, including the functions of non-coding RNA (ncRNAs), require more extensive investigation. In this study, high throughput transcriptome sequencing (RNA-seq) was used to identify differentially expressed lncRNAs and mRNAs in normal, cervical intraepithelial neoplasia and cervical cancer tissues from Uyghur women in western China. Dysregulated lncRNAs were found to extensively participate in cervical cancer development, including viral carcinogenesis, cell cycle and cytokine-cytokine receptor signaling. Two miRNA-host lncRNAs, LINC00925 and MIR155HG, showed elevated expression in cervical cancer samples, but prolonged the survival time of cervical cancer patients. The 2 mature miRNAs of the above 2 lncRNAs, miR-9 and miR-155, also showed similar features in cervical cancer. In addition, we identified 545 lncRNAs with potential functions in regulating these 2 miRNAs as competing endogenous RNAs (ceRNAs). In summary, our study demonstrated the dysregulated lncRNAs/miRNAs, particularly LINC00925/miR-9 and MIR155HG/miR-155, regulate the development of cervical cancer by forming a interaction network with mRNAs, highlighting the importance of elucidating the underlying mechanisms of ncRNAs in cervical cancer development.
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Pinheiro, Amanda, and Francisco J. Naya. "The Key Lnc (RNA)s in Cardiac and Skeletal Muscle Development, Regeneration, and Disease." Journal of Cardiovascular Development and Disease 8, no. 8 (July 25, 2021): 84. http://dx.doi.org/10.3390/jcdd8080084.
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Non-coding RNAs (ncRNAs) play a key role in the regulation of transcriptional and epigenetic activity in mammalian cells. Comprehensive analysis of these ncRNAs has revealed sophisticated gene regulatory mechanisms which finely tune the proper gene output required for cellular homeostasis, proliferation, and differentiation. However, this elaborate circuitry has also made it vulnerable to perturbations that often result in disease. Among the many types of ncRNAs, long non-coding RNAs (lncRNAs) appear to have the most diverse mechanisms of action including competitive binding to miRNA targets, direct binding to mRNA, interactions with transcription factors, and facilitation of epigenetic modifications. Moreover, many lncRNAs display tissue-specific expression patterns suggesting an important regulatory role in organogenesis, yet the molecular mechanisms through which these molecules regulate cardiac and skeletal muscle development remains surprisingly limited. Given the structural and metabolic similarities of cardiac and skeletal muscle, it is likely that several lncRNAs expressed in both of these tissues have conserved functions in establishing the striated muscle phenotype. As many aspects of regeneration recapitulate development, understanding the role lncRNAs play in these processes may provide novel insights to improve regenerative therapeutic interventions in cardiac and skeletal muscle diseases. This review highlights key lncRNAs that function as regulators of development, regeneration, and disease in cardiac and skeletal muscle. Finally, we highlight lncRNAs encoded by imprinted genes in striated muscle and the contributions of these loci on the regulation of gene expression.
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Greco, Simona, Carlo Gaetano, and Fabio Martelli. "Long Noncoding Competing Endogenous RNA Networks in Age-Associated Cardiovascular Diseases." International Journal of Molecular Sciences 20, no. 12 (June 24, 2019): 3079. http://dx.doi.org/10.3390/ijms20123079.
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Cardiovascular diseases (CVDs) are the most serious health problem in the world, displaying high rates of morbidity and mortality. One of the main risk factors for CVDs is age. Indeed, several mechanisms are at play during aging, determining the functional decline of the cardiovascular system. Aging cells and tissues are characterized by diminished autophagy, causing the accumulation of damaged proteins and mitochondria, as well as by increased levels of oxidative stress, apoptosis, senescence and inflammation. These processes can induce a rapid deterioration of cellular quality-control systems. However, the molecular mechanisms of age-associated CVDs are only partially known, hampering the development of novel therapeutic strategies. Evidence has emerged indicating that noncoding RNAs (ncRNAs), such as long ncRNAs (lncRNAs) and micro RNAs (miRNAs), are implicated in most patho-physiological mechanisms. Specifically, lncRNAs can bind miRNAs and act as competing endogenous-RNAs (ceRNAs), therefore modulating the levels of the mRNAs targeted by the sponged miRNA. These complex lncRNA/miRNA/mRNA networks, by regulating autophagy, apoptosis, necrosis, senescence and inflammation, play a crucial role in the development of age-dependent CVDs. In this review, the emerging knowledge on lncRNA/miRNA/mRNA networks will be summarized and the way in which they influence age-related CVDs development will be discussed.
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Ge, Changhui, Fei Su, Hanjiang Fu, Yuan Wang, Baolei Tian, Bin Liu, Jie Zhu, Yong Ding, and Xiaofei Zheng. "RNA Profiling Reveals a Common Mechanism of Histone Gene Downregulation and Complementary Effects for Radioprotectants in Response to Ionizing Radiation." Dose-Response 18, no. 4 (October 1, 2020): 155932582096843. http://dx.doi.org/10.1177/1559325820968433.
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High-dose ionizing radiation (IR) alters the expression levels of non-coding RNAs (ncRNAs). However, the roles of ncRNAs and mRNAs in mediating radiation protection by radioprotectants remain unknown. Microarrays were used to determine microRNA (miRNA), long ncRNA (lncRNA), and mRNA expression profiles in the bone marrow of irradiated mice pretreated with amifostine, CBLB502, and nilestriol. Differentially expressed mRNAs were functionally annotated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Some histone cluster genes were validated by real-time PCR, and the effects of radioprotectant combinations were monitored by survival analysis. We found that these radioprotectants increased the induction of lncRNAs and mRNAs. miRNA, lncRNA, and mRNA expression patterns were similar with amifostine and CBLB502, but not nilestriol. The radioprotectants exhibited mostly opposite effects against IR-induced miRNAs, lncRNAs, and mRNAs while inducing a common histone gene downregulation following IR, mainly via nucleosome assembly and related signaling pathways. Notably, the effects of nilestriol significantly complemented those of amisfostine or CBLB502; low-dose drug combinations resulted in better radioprotective effects in pretreated mice. Thus, we present histone gene downregulation by radioprotectants, together with the biological functions of miRNA, lncRNA, and mRNA, to explain the mechanism underlying radioprotection.
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Mosca, Laura, Francesca Vitiello, Luigi Borzacchiello, Alessandra Coppola, Roberta Veglia Tranchese, Martina Pagano, Michele Caraglia, Giovanna Cacciapuoti, and Marina Porcelli. "Mutual Correlation between Non-Coding RNA and S-Adenosylmethionine in Human Cancer: Roles and Therapeutic Opportunities." Cancers 13, no. 13 (June 29, 2021): 3264. http://dx.doi.org/10.3390/cancers13133264.
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Epigenetics includes modifications in DNA methylation, histone and chromatin structure, and expression of non-coding RNAs (ncRNAs), especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Knowledge of the relationships between S-adenosylmethionine (AdoMet or SAM), the universal methyl donor for all epigenetic methylation reactions and miRNAs or lncRNAs in human cancer may provide helpful insights for the development of new end more effective anticancer therapeutic approaches. In recent literature, a complex network of mutual interconnections between AdoMet and miRNAs or lncRNAs has been reported and discussed. Indeed, ncRNAs expression may be regulated by epigenetic mechanisms such as DNA and RNA methylation and histone modifications. On the other hand, miRNAs or lncRNAs may influence the epigenetic apparatus by modulating the expression of its enzymatic components at the post-transcriptional level. Understanding epigenetic mechanisms, such as dysregulation of miRNAs/lncRNAs and DNA methylation, has become of central importance in modern research. This review summarizes the recent findings on the mechanisms by which AdoMet and miRNA/lncRNA exert their bioactivity, providing new insights to develop innovative and more efficient anticancer strategies based on the interactions between these epigenetic modulators.
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Erdem, Mustafa Genco, Ozge Unlu, and Mehmet Demirci. "Could Long Non-Coding RNA MEG3 and PTENP1 Interact with miR-21 in the Pathogenesis of Non-Alcoholic Fatty Liver Disease?" Biomedicines 11, no. 2 (February 15, 2023): 574. http://dx.doi.org/10.3390/biomedicines11020574.
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NAFLD is the most common cause of chronic liver disease worldwide. The miRNAs and lncRNAs are important endogenous ncRNAs families that can regulate molecular mechanisms. The aim of this study was to analyze the miRNA and lncRNA expression profiles in serum samples of NAFLD patients with different types of hepatosteatosis compared to healthy controls by the qPCR method. A total of180 NAFLD patients and 60 healthy controls were included. miRCURY LNA miRNA miRNome PCR human panel I + II kit and LncProfiler qPCR Array Kit were used to detect miRNA and lncRNA expression, respectively. DIANA miRPath and DIANA-lncBase web servers were used for interaction analysis. As a result, 75 miRNA and 24 lncRNA expression changes were determined. For miRNAs and lncRNAs, 30 and 5 were downregulated and 45 and 19 were upregulated, respectively. hsa-miR-21 was upregulated 2-fold whereas miR-197 was downregulated 0.25-fold. Among lncRNAs, NEAT1 was upregulated 2.9-fold while lncRNA MEG3 was downregulated 0.41-fold. A weak correlation was found between hsa-miR-122 and lncRNA MALAT1. As a conclusion, it is clear that lncRNA–miRNA interaction is involved in the molecular mechanisms of the emergence of NAFLD. The lncRNAs MEG3 and PTENP1 interacted with hsa-miR-21. It was thought that this interaction should be investigated as a biomarker for the development of NAFLD.
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Rodriguez, Princess D., Hana Paculova, Sophie Kogut, Jessica Heath, Hilde Schjerven, and Seth Frietze. "Non-Coding RNA Signatures of B-Cell Acute Lymphoblastic Leukemia." International Journal of Molecular Sciences 22, no. 5 (March 7, 2021): 2683. http://dx.doi.org/10.3390/ijms22052683.
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Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell acute lymphoblastic leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.
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Natarelli, Lucia, and Christian Weber. "A Non-Canonical Link between Non-Coding RNAs and Cardiovascular Diseases." Biomedicines 10, no. 2 (February 14, 2022): 445. http://dx.doi.org/10.3390/biomedicines10020445.
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Cardiovascular diseases (CVDs) are among the top leading causes of mortality worldwide. Besides canonical environmental and genetic changes reported so far for CVDs, non-coding RNAs (ncRNAs) have emerged as key regulators of genetic and epigenetic mechanisms involved in CVD progression. High-throughput and sequencing data revealed that almost 80% of the total genome not only encodes for canonical ncRNAs, such as micro and long ncRNAs (miRNAs and lncRNAs), but also generates novel non-canonical sub-classes of ncRNAs, such as isomiRs and miRNA- and lncRNA-like RNAs. Moreover, recent studies reveal that canonical ncRNA sequences can influence the onset and evolution of CVD through novel “non-canonical” mechanisms. However, a debate exists over the real existence of these non-canonical ncRNAs and their concrete biochemical functions, with most of the dark genome being considered as “junk RNA”. In this review, we report on the ncRNAs with a scientifically validated canonical and non-canonical biogenesis. Moreover, we report on canonical ncRNAs that play a role in CVD through non-canonical mechanisms of action.
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Chen, Chong, Haining Tan, Jiaqi Bi, Zheng Li, Tianhua Rong, Youxi Lin, Liang Sun, Xingye Li, and Jianxiong Shen. "Identification of Competing Endogenous RNA Regulatory Networks in Vitamin A Deficiency-Induced Congenital Scoliosis by Transcriptome Sequencing Analysis." Cellular Physiology and Biochemistry 48, no. 5 (2018): 2134–46. http://dx.doi.org/10.1159/000492556.
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Background/Aims: Congenital scoliosis (CS) is a result of anomalous development of vertebrae and is frequently associated with somitogenesis malformation. Although noncoding RNAs (ncRNAs) have been recently determined to be involved in the pathogenesis of CS, the competing endogenous RNA (ceRNA) regulatory networks in CS remain largely unknown. Methods: Sequencing was conducted to explore the ncRNA expression profiles in rat embryos (gestation day 9) following vitamin A deficiency (VAD) (n = 9 for the vitamin A deficiency-induced congenital scoliosis (VAD-CS) group and n = 4 for the control group). Real-time reverse transcriptase polymerase chain reaction (RT-PCR) was conducted to verify the expression levels of selected mRNAs, long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs). Bioinformatics analysis was used to discover the possible relationships and functions of the ceRNAs. Results: A total of 749 mRNAs, 56 miRNAs, 685 lncRNAs, and 70 circRNAs were identified to have significantly different expression levels in the two groups. Wnt, PI3K-ATK, FoxO, EGFR, and mTOR were found to be the most significant pathways involved in VAD-CS pathogenesis. The circRNA/miRNA/mRNA and lncRNA/miRNA/mRNA networks of CS were built, and the gene expression mechanisms regulated by ncRNAs were unveiled via the ceRNA regulatory networks. Conclusion: We comprehensively identified ceRNA regulatory networks of embryonic somite development in VAD-CS as well as revealed the contribution of different ncRNA expression profiles. Our data demonstrate the association between mRNAs and ncRNAs in the pathogenic mechanism of CS.
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Mondal, Priya, Jagadish Natesh, Mohammad Amjad Kamal, and Syed Musthapa Meeran. "Non-coding RNAs in Lung Cancer Chemoresistance." Current Drug Metabolism 20, no. 13 (January 23, 2020): 1023–32. http://dx.doi.org/10.2174/1389200221666200106105201.
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Background: Lung cancer is the leading cause of cancer-associated death worldwide with limited treatment options. The major available treatment options are surgery, radiotherapy, chemotherapy and combinations of these treatments. In chemotherapy, tyrosine kinase inhibitors and taxol are the first lines of chemotherapeutics used for the treatment of lung cancer. Often drug resistance in the clinical settings hinders the efficiency of the treatment and intrigues the tumor relapse. Drug-resistance is triggered either by intrinsic factors or due to the prolonged cycles of chemotherapy as an acquired-resistance. There is an emerging role of non-coding RNAs (ncRNAs), including notorious microRNAs (miRNAs), proposed to be actively involved in the regulations of various tumor-suppressor genes and oncogenes. Result: The altered gene expression by miRNA is largely mediated either by the degradation or by interfering with the translation of targeted mRNA. Unlike miRNA, other type of ncRNAs, such as long non-coding RNAs (lncRNAs), can target the transcriptional activator or the repressor, RNA polymerase, and even DNA-duplex to regulate the gene expressions. Many studies have confirmed the crucial role of ncRNAs in lung adenocarcinoma progression and importantly, in the acquisition of chemoresistance. Recently, ncRNAs have become early biomarkers and therapeutic targets for lung cancer. Conclusion: Targeting ncRNAs could be an effective approach for the development of novel therapeutics against lung cancer and to overcome the chemoresistance.
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Teng, Xiangnan, Jing Liao, Lili Zhao, Wei Dong, Haiyi Xue, Lang Bai, and Shanling Xu. "Whole transcriptome analysis of the differential RNA profiles and associated competing endogenous RNA networks in LPS-induced acute lung injury (ALI)." PLOS ONE 16, no. 5 (May 7, 2021): e0251359. http://dx.doi.org/10.1371/journal.pone.0251359.
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Acute lung injury (ALI) is a serious inflammation disease usually arises alveolar epithelial membrane dysfunction and even causes death. Therefore, the aims of this study are to screen the differentially expressed lncRNAs, circRNAs, miRNAs, and mRNAs in ALI based on the high-throughput sequencing. The lipopolysaccharide (LPS)-induced ALI mouse model was established, the injury of ALI mouse model was evaluated through histological analysis with hemotoxylin and eosin (H & E) staining assay, dry/wet ratio, infiltrated-immune cells, ET-1 mRNA expression and released-proinflammation factors. Then, expression data of lncRNAs, circRNAs, miRNAs and mRNAs in ALI were acquired using whole-transcriptome sequencing. The differential expression of lncRNAs (DE lncRNAs), circRNAs (DE circRNAs), miRNAs (DE miRNAs) and mRNAs (DE mRNAs) were identified, and the lncRNA-miRNA-mRNA network and circRNA-miRNA-mRNA network were constructed, and the biological function of target genes were annotated based on bioinformatics analysis. In the present study, the LPS-induced ALI mouse model was successfully established. The biological analysis results showed that total 201 DE lncRNAs, 172 DE circRNAs, 62 DE miRNAs, and 3081 DE mRNAs were identified in ALI. The 182 lncRNA-miRNA-mRNA networks and 32 circRNA-miRNA-mRNA networks were constructed were constructed based on the correlation between lncRNAs/circRNAs, miRNAs, mRNAs. The biological function analysis indicated that TNF signaling pathway, chemokine signaling pathway and so on involved in ALI. In the present study, the differential expression coding and non-coding RNAs (ncRNAs) in ALI were identified, and their regulatory networks were constructed. There might provide the potential biomarkers and underlying mechanism for ALI diagnosis and treatment.
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Dhingra, Sourabh. "Role of Non-coding RNAs in Fungal Pathogenesis and Antifungal Drug Responses." Current Clinical Microbiology Reports 7, no. 4 (October 2, 2020): 133–41. http://dx.doi.org/10.1007/s40588-020-00151-7.
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Abstract Purpose of Review Non-coding RNAs (ncRNAs), including regulatory small RNAs (sRNAs) and long non-coding RNAs (lncRNAs), constitute a significant part of eukaryotic genomes; however, their roles in fungi are just starting to emerge. ncRNAs have been shown to regulate gene expression in response to varying environmental conditions (like stress) and response to chemicals, including antifungal drugs. In this review, I highlighted recent studies focusing on the functional roles of ncRNAs in pathogenic fungi. Recent Findings Emerging evidence suggests sRNAs (small RNAs) and lncRNAs (long non-coding RNAs) play an important role in fungal pathogenesis and antifungal drug response. Their roles include posttranscriptional gene silencing, histone modification, and chromatin remodeling. Fungal pathogens utilize RNA interference (RNAi) mechanisms to regulate pathogenesis-related genes and can also transfer sRNAs inside the host to suppress host immunity genes to increase virulence. Hosts can also transfer sRNAs to induce RNAi in fungal pathogens to reduce virulence. Additionally, sRNAs and lncRNAs also regulate gene expression in response to antifungal drugs increasing resistance (and possibly tolerance) to drugs. Summary Herein, I discuss what is known about ncRNAs in fungal pathogenesis and antifungal drug responses. Advancements in genomic technologies will help identify the ncRNA repertoire in fungal pathogens, and functional studies will elucidate their mechanisms. This will advance our understanding of host-fungal interactions and potentially help develop better treatment strategies.
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Malek, Ehsan, Tahir Latif, Anil Goud Jegga, Sajjeev Jagannathan, Nikhil Vad, Mohamed A. Y. Abdel Malek, and James J. Driscoll. "Correlation of Non-Coding RNA Expression with Response to Proteasome Inhibitors in Multiple Myeloma." Blood 124, no. 21 (December 6, 2014): 3415. http://dx.doi.org/10.1182/blood.v124.21.3415.3415.
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Abstract Background: Multiple myeloma (MM) is a heterogeneous diseaseand there is an increased need for more accurate risk classification methods to improve treatment decision-making because of its high impact on clinical outcomes. Here, we demonstrate evidence to support the prognostic value of non-coding RNAs (ncRNAs) as newly discovered genetic biomarkers of drug-resistant and/or high-risk forms of MM. NcRNAs, e.g., long ncRNAs (lncRNAs) and microRNAs (miRNAs), act as positive or negative regulators of gene expression to control cell proliferation, apoptosis and drug resistance. NcRNAs have been shown to play a role in both solid and hematological tumors. Stratification of MM based upon cytogenetic abnormalities and protein-coding gene signatures does not adequately correlate with the depth and durability of response to novel agents such as bortezomib. Therefore, ncRNAs as new class of molecular effectors may enhance the basic understanding of myelomagenesis and provide better stratification of myeloma subtypes. To investigate the role of ncRNAs in resistance to proteasome inhibitors (PIs), we compared global ncRNA profiling in drug-naïve cells to cells with acquired resistance to the PIs bortezomib, carfilzomib and ixazomib. We hypothesized that ncRNAs commonly deregulated in the 3 resistant cell lines would yield a ncRNA signature and novel therapeutic targets. Experimental Procedures: RPMI 8226 cells resistant to PIs were generated through successive exposure to bortezomib, carfilzomib or ixazomib over a period of 6 months. Total RNA was isolated and genome-wide ncRNA expression profiling was performed using Affymetrix3.0 microarray chips that contained nearly 40,000 miRNA and 13,300 lncRNA probes. NcRNA expression profiles from drug-resistant cells were compared to that of drug- naïve parental cells treated with vehicle alone using the same treatment algorithm. Housekeeping genes were used for log expression normalization. MM patients' bone marrow aspirates were obtained from patients after University of Cincinnati Institutional Review Board approval. Results: Bioinformatic analysis of the ncRNA profiles identified a panel of 87 lncRNAs and ~40 miRNAs that were significantly (>100-fold) deregulated in all three drug-resistant cell lines relative to drug- naïve parental cells. Strikingly, ~90% of the deregulated lncRNAs exhibited a similar expression pattern in all 3 PI-resistant cell lines. Twenty lncRNAs were deregulated > 1000-fold in all 3 resistant cell lines (Figure 1). RPMI 8226 cells carry a chromosomal (14,16) translocation. Interestingly, none of the deregulated lncRNAs detected here localized to chromosome 14 or 16, suggestive of a cytogenetic-independent mechanism of drug resistance. The lncRNA COL4A-2A was upregulated >5,000-fold in resistant cells and displayed extensive sequence complementarity to miRNA-29 that was downregulated in resistant cells. Also, our microarray-based studies have identified ncRNAs deregulated in MM patient tumor samples relative to normal plasma cells from healthy age-matched individuals. A significant number of the deregulated ncRNAs between drug- naïve and drug resistant cells were also deregulated in normal plasma cells relative to myeloma cells. Studies are correlating the ncRNA patterns seen in drug-sensitive and drug-resistant cell lines with ncRNA patterns obtained from malignant plasma cells of patients currently receiving bortezomib-based therapy. Updated results to correlate ncRNA expression with myeloma patient response to bortezomib will be presented.Conclusions: Taken together, we have identified a curated panel of ncRNAs deregulated in common within myeloma cells generated with acquired resistant to three different clinically-relevant proteasome inhibitors. Ongoing studies will correlate ncRNA expression patterns from resistant cells with patterns generated from patients with monoclonal gammopathy of unknown significance (MGUS), Smoldering MM, newly diagnosed MM, refractory disease and plasma cell leukemia. In addition, ncRNA patterns will be generated based upon MM patient response to bortezomib. Further investigation is warranted to shed light on the role of these ncRNAs in the development of MM, to identify their targets and to define their role in drug resistance. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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Liu, Jian-Bo, Jia-Bao Zhang, Xiang-Min Yan, Peng-Gui Xie, Yao Fu, Xu-Huang Fu, Xu-Lei Sun, et al. "DNA Double-Strand Break-Related Competitive Endogenous RNA Network of Noncoding RNA in Bovine Cumulus Cells." Genes 14, no. 2 (January 22, 2023): 290. http://dx.doi.org/10.3390/genes14020290.
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(1) Background: DNA double strand breaks (DSBs) are the most serious form of DNA damage that affects oocyte maturation and the physiological state of follicles and ovaries. Non-coding RNAs (ncRNAs) play a crucial role in DNA damage and repair. This study aims to analyze and establish the network of ncRNAs when DSB occurs and provide new ideas for next research on the mechanism of cumulus DSB. (2) Methods: Bovine cumulus cells (CCs) were treated with bleomycin (BLM) to construct a DSB model. We detected the changes of the cell cycle, cell viability, and apoptosis to determine the effect of DSBs on cell biology, and further evaluated the relationship between the transcriptome and competitive endogenous RNA (ceRNA) network and DSBs. (3) Results: BLM increased γH2AX positivity in CCs, disrupted the G1/S phase, and decreased cell viability. Totals of 848 mRNAs, 75 long noncoding RNAs (lncRNAs), 68 circular RNAs (circRNAs), and 71 microRNAs (miRNAs) in 78 groups of lncRNA–miRNA–mRNA regulatory networks, 275 groups of circRNA–miRNA–mRNA regulatory networks, and five groups of lncRNA/circRNA–miRNA–mRNA co-expression regulatory networks were related to DSBs. Most differentially expressed ncRNAs were annotated to cell cycle, p53, PI3K-AKT, and WNT signaling pathways. (4) Conclusions: The ceRNA network helps to understand the effects of DNA DSBs activation and remission on the biological function of CCs.
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Riaz, Farooq, and Dongmin Li. "Non-coding RNA Associated Competitive Endogenous RNA Regulatory Network: Novel Therapeutic Approach in Liver Fibrosis." Current Gene Therapy 19, no. 5 (December 27, 2019): 305–17. http://dx.doi.org/10.2174/1566523219666191107113046.
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Liver fibrosis or scarring is the most common pathological feature caused by chronic liver injury, and is widely considered one of the primary causes of morbidity and mortality. It is primarily characterised by hepatic stellate cells (HSC) activation and excessive extracellular matrix (ECM) protein deposition. Overwhelming evidence suggests that the dysregulation of several noncoding RNAs (ncRNAs), mainly long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs) contributes to the activation of HSC and progression of liver fibrosis. These ncRNAs not only bind to their target genes for the development and regression of liver fibrosis but also act as competing endogenous RNAs (ceRNAs) by sponging with miRNAs to form signaling cascades. Among these signaling cascades, lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA are critical modulators for the initiation, progression, and regression of liver fibrosis. Thus, targeting these interacting ncRNA cascades can serve as a novel and potential therapeutic target for inhibition of HSC activation and prevention and regression of liver fibrosis.
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da Silveira, Willian A., Ludivine Renaud, Edward S. Hazard, and Gary Hardiman. "miRNA and lncRNA Expression Networks Modulate Cell Cycle and DNA Repair Inhibition in Senescent Prostate Cells." Genes 13, no. 2 (January 24, 2022): 208. http://dx.doi.org/10.3390/genes13020208.
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Cellular senescence is a state of permanent growth arrest that arises once cells reach the limit of their proliferative capacity. It creates an inflammatory microenvironment favouring the initiation and progression of various age-related diseases, including prostate cancer. Non-coding RNAs (ncRNAs) have emerged as important regulators of cellular gene expression. Nonetheless, very little is known about the interplay of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) and how deregulation of ncRNA networks promotes cellular senescence. To investigate this, human prostate epithelial cells were cultured through different passages until senescent, and their RNA was extracted and sequenced using RNA sequencing (RNAseq) and microRNA sequencing (miRNA-seq) miRNAseq. Differential expression (DE) gene analysis was performed to compare senescent and proliferating cells with Limma, miRNA-target interactions with multiMiR, lncRNA-target interactions using TCGA data and network evaluation with miRmapper. We found that miR-335-3p, miR-543 and the lncRNAs H19 and SMIM10L2A all play central roles in the regulation of cell cycle and DNA repair processes. Expression of most genes belonging to these pathways were down-regulated by senescence. Using the concept of network centrality, we determined the top 10 miRNAs and lncRNAs, with miR-335-3p and H19 identified as the biggest hubs for miRNAs and lncRNA respectively. These ncRNAs regulate key genes belonging to pathways involved in cell senescence and prostate cancer demonstrating their central role in these processes and opening the possibility for their use as biomarkers or therapeutic targets to mitigate against prostate ageing and carcinogenesis.
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Rajtmajerová, Marie, Andriy Trailin, Václav Liška, Kari Hemminki, and Filip Ambrozkiewicz. "Long Non-Coding RNA and microRNA Interplay in Colorectal Cancer and Their Effect on the Tumor Microenvironment." Cancers 14, no. 21 (November 5, 2022): 5450. http://dx.doi.org/10.3390/cancers14215450.
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As the current staging and grading systems are not sufficient to stratify patients for therapy and predict the outcome of the disease, there is an urgent need to understand cancer in its complexity. The mutual relationship between tumour and immune or stromal cells leads to rapid evolution and subsequent genetic and epigenetic changes. Immunoscore has been introduced as a diagnostic tool for colorectal cancer (CRC) only recently, emphasising the role of the specific tumor microenvironment in patient’s prognosis and overall outcome. Despite the fact that non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), cannot be translated into proteins, they significantly affect cell’s transcriptome and translatome. miRNA binding to mRNA efficiently blocks its translation and leads to mRNA destruction. On the other hand, miRNAs can be bound by lncRNAs or circular RNAs (circRNAs), which prevents them from interfering with translation. In this way, ncRNAs create a multi-step network that regulates the cell’s translatome. ncRNAs are also shed by the cell as exogenous RNAs and they are also found in exosomes, suggesting their role in intercellular communication. Hence, these mechanisms affect the tumor microenvironment as much as protein signal molecules. In this review, we provide an insight into the current knowledge of the microenvironment, lncRNAs’, and miRNAs’ interplay. Understanding mechanisms that underlie the evolution of a tissue as complex as a tumour is crucial for the future success in therapy.
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Han, Tae-Su, Keun Hur, Hyun-Soo Cho, and Hyun Seung Ban. "Epigenetic Associations between lncRNA/circRNA and miRNA in Hepatocellular Carcinoma." Cancers 12, no. 9 (September 14, 2020): 2622. http://dx.doi.org/10.3390/cancers12092622.
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The three major members of non-coding RNAs (ncRNAs), named microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play an important role in hepatocellular carcinoma (HCC) development. Recently, the competing endogenous RNA (ceRNA) regulation model described lncRNA/circRNA as a sponge for miRNAs to indirectly regulate miRNA downstream target genes. Accumulating evidence has indicated that ceRNA regulatory networks are associated with biological processes in HCC, including cancer cell growth, epithelial to mesenchymal transition (EMT), metastasis, and chemoresistance. In this review, we summarize recent discoveries, which are specific ceRNA regulatory networks (lncRNA/circRNA-miRNA-mRNA) in HCC and discuss their clinical significance.
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Siniscalchi, Chiara, Armando Di Palo, Aniello Russo, and Nicoletta Potenza. "The lncRNAs at X Chromosome Inactivation Center: Not Just a Matter of Sex Dosage Compensation." International Journal of Molecular Sciences 23, no. 2 (January 6, 2022): 611. http://dx.doi.org/10.3390/ijms23020611.
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Non-coding RNAs (ncRNAs) constitute the majority of the transcriptome, as the result of pervasive transcription of the mammalian genome. Different RNA species, such as lncRNAs, miRNAs, circRNA, mRNAs, engage in regulatory networks based on their reciprocal interactions, often in a competitive manner, in a way denominated “competing endogenous RNA (ceRNA) networks” (“ceRNET”): miRNAs and other ncRNAs modulate each other, since miRNAs can regulate the expression of lncRNAs, which in turn regulate miRNAs, titrating their availability and thus competing with the binding to other RNA targets. The unbalancing of any network component can derail the entire regulatory circuit acting as a driving force for human diseases, thus assigning “new” functions to “old” molecules. This is the case of XIST, the lncRNA characterized in the early 1990s and well known as the essential molecule for X chromosome inactivation in mammalian females, thus preventing an imbalance of X-linked gene expression between females and males. Currently, literature concerning XIST biology is becoming dominated by miRNA associations and they are also gaining prominence for other lncRNAs produced by the X-inactivation center. This review discusses the available literature to explore possible novel functions related to ceRNA activity of lncRNAs produced by the X-inactivation center, beyond their role in dosage compensation, with prospective implications for emerging gender-biased functions and pathological mechanisms.
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Shi, Jun, Guangqiang Ye, Guoliang Zhao, Xuedong Wang, Chunhui Ye, Keooudone Thammavong, Jing Xu, and Jiahong Dong. "Coordinative control of G2/M phase of the cell cycle by non-coding RNAs in hepatocellular carcinoma." PeerJ 6 (October 16, 2018): e5787. http://dx.doi.org/10.7717/peerj.5787.
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Objective To investigate the interaction of non-coding RNAs (ncRNAs) in hepatocellular carcinoma. Methods We compared the ncRNAs and mRNAs expression profiles of hepatocellular carcinoma and adjacent tissue by microarray and RT-PCR. The relationship between different ncRNAs and mRNA was analyzed using bioinformatics tools. A regulatory model of ncRNAs in hepatocellular carcinoma cells was developed. Results A total of 1,704 differentially expressed lncRNAs, 57 miRNAs, and 2,093 mRNAs were identified by microarray analyses. There is a co-expression relationship between two ncRNAs (miRNA-125b-2-3p and lncRNA P26302). Bioinformatics analysis demonstrated cyclin-dependent kinases 1 and CyclinA2 as potential targets of miR-125b-2-3p and Polo-like kinase 1 as potential target of lncRNAP26302. All three gene are important components in the G2/M phase of cell cycle. Subsequently real-time polymerase chain reaction (PCR) studies confirmed these microarray results. Conclusion MiR-125b-2-3p and lncRNAP26302 may affect the G2/M phase of the cell cycle through the regulation of their respective target genes. This study shows a role of ncRNAs in pathogenesis of hepatocellular carcinoma at molecular level, providing a basis for the future investigation aiming at early diagnosis and novel treatment of hepatocellular carcinoma.
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Ye, Junhong, Jifu Li, and Ping Zhao. "Roles of ncRNAs as ceRNAs in Gastric Cancer." Genes 12, no. 7 (July 2, 2021): 1036. http://dx.doi.org/10.3390/genes12071036.
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Although ignored in the past, with the recent deepening of research, significant progress has been made in the field of non-coding RNAs (ncRNAs). Accumulating evidence has revealed that microRNA (miRNA) response elements regulate RNA. Long ncRNAs, circular RNAs, pseudogenes, miRNAs, and messenger RNAs (mRNAs) form a competitive endogenous RNA (ceRNA) network that plays an essential role in cancer and cardiovascular, neurodegenerative, and autoimmune diseases. Gastric cancer (GC) is one of the most common cancers, with a high degree of malignancy. Considerable progress has been made in understanding the molecular mechanism and treatment of GC, but GC’s mortality rate is still high. Studies have shown a complex ceRNA crosstalk mechanism in GC. lncRNAs, circRNAs, and pseudogenes can interact with miRNAs to affect mRNA transcription. The study of the involvement of ceRNA in GC could improve our understanding of GC and lead to the identification of potential effective therapeutic targets. The research strategy for ceRNA is mainly to screen the different miRNAs, lncRNAs, circRNAs, pseudogenes, and mRNAs in each sample through microarray or sequencing technology, predict the ceRNA regulatory network, and, finally, conduct functional research on ceRNA. In this review, we briefly discuss the proposal and development of the ceRNA hypothesis and the biological function and principle of ceRNAs in GC, and briefly introduce the role of ncRNAs in the GC’s ceRNA network.
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Magagula, Loretta, Maria Gagliardi, Jerolen Naidoo, and Musa Mhlanga. "Lnc-ing inflammation to disease." Biochemical Society Transactions 45, no. 4 (July 7, 2017): 953–62. http://dx.doi.org/10.1042/bst20160377.
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Termed ‘master gene regulators’ long ncRNAs (lncRNAs) have emerged as the true vanguard of the ‘noncoding revolution’. Functioning at a molecular level, in most if not all cellular processes, lncRNAs exert their effects systemically. Thus, it is not surprising that lncRNAs have emerged as important players in human pathophysiology. As our body's first line of defense upon infection or injury, inflammation has been implicated in the etiology of several human diseases. At the center of the acute inflammatory response, as well as several pathologies, is the pleiotropic transcription factor NF-κβ. In this review, we attempt to capture a summary of lncRNAs directly involved in regulating innate immunity at various arms of the NF-κβ pathway that have also been validated in human disease. We also highlight the fundamental concepts required as lncRNAs enter a new era of diagnostic and therapeutic significance.
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Xiong, Wei, Yan Qu, Hongmei Chen, and Jinqiao Qian. "Insight into long noncoding RNA–miRNA–mRNA axes in myocardial ischemia-reperfusion injury: the implications for mechanism and therapy." Epigenomics 11, no. 15 (November 1, 2019): 1733–48. http://dx.doi.org/10.2217/epi-2019-0119.
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Emerging evidence has demonstrated that regulatory noncoding RNAs (ncRNAs), such as long noncoding RNAs (lncRNAs) and miRNAs, play crucial roles in the initiation and progress of myocardial ischemia-reperfusion injury (MIRI), which is associated with autophagy, apoptosis and necrosis of cardiomyocytes, as well as oxidative stress, inflammation and mitochondrial dysfunction. LncRNAs serve as a precursor or host of miRNAs and directly/indirectly affecting miRNAs via competitive binding or sponge effects. Simultaneously, miRNAs post-transcriptionally regulate the expression of genes by targeting various mRNA sequences due to their imperfect pairing with mRNAs. This review summarizes the potential regulatory role of lncRNA–miRNA–mRNA axes in MIRI and related molecular mechanisms of cardiac disorders, also provides insight into the potential therapies for MIRI-induced diseases.
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Li, Congcong, Haoyuan Han, Xiuling Li, Jiao Wu, Xinfeng Li, Hui Niu, and Wantao Li. "Analysis of lncRNA, miRNA, and mRNA Expression Profiling in Type I IFN and Type II IFN Overexpressed in Porcine Alveolar Macrophages." International Journal of Genomics 2021 (June 16, 2021): 1–28. http://dx.doi.org/10.1155/2021/6666160.
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Current data is scarce regarding the function of noncoding RNAs (ncRNAs) such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) in the interferon- (IFN-) mediated immune response. This is a comprehensive study that analyzes the lncRNA and miRNA expression profiles of the type I IFN and type II IFN in porcine alveolar macrophages using RNA sequencing. There was a total of 152 overexpressed differentially expressed (DE) lncRNAs and 21 DE miRNAs across type I IFN and type II IFN in porcine alveolar macrophages. Subsequent lncRNA-miRNA-mRNA network construction revealed the involvement of 36 DE lncRNAs and 12 DE miRNAs. LncRNAs such as the XLOC_211306, XLOC_100516, XLOC_00695, XLOC_149196, and XLOC_014459 were expressed at a higher degree in the type I IFN group, while XLOC_222640, XLOC_047290, XLOC_147777, XLOC_162298, XLOC_220210, and XLOC_165237 were expressed at a higher degree in the type II IFN group. These lncRNAs were found to act as “sponges” for miRNAs such as miR-34a, miR-328, miR-885-3p, miR-149, miR-30c-3p, miR-30b-5p, miR-708-5p, miR-193a-5p, miR-365-5p, and miR-7. Their target genes FADS2, RPS6KA1, PIM1, and NOD1 were found to be associated with several immune-related signaling pathways including the NOD-like receptor, Jak-STAT, mTOR, and PPAR signaling pathways. These experiments provide a comprehensive profile of overexpressed noncoding RNAs in porcine alveolar macrophages, providing new insights regarding the IFN-mediated immune response.
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Matboli, Marwa, Shaimaa H. Gadallah, Wafaa M. Rashed, Amany Helmy Hasanin, Nada Essawy, Hala M. Ghanem, and Sanaa Eissa. "mRNA-miRNA-lncRNA Regulatory Network in Nonalcoholic Fatty Liver Disease." International Journal of Molecular Sciences 22, no. 13 (June 24, 2021): 6770. http://dx.doi.org/10.3390/ijms22136770.
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Aim: we aimed to construct a bioinformatics-based co-regulatory network of mRNAs and non coding RNAs (ncRNAs), which is implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), followed by its validation in a NAFLD animal model. Materials and Methods: The mRNAs–miRNAs–lncRNAs regulatory network involved in NAFLD was retrieved and constructed utilizing bioinformatics tools. Then, we validated this network using an NAFLD animal model, high sucrose and high fat diet (HSHF)-fed rats. Finally, the expression level of the network players was assessed in the liver tissues using reverse transcriptase real-time polymerase chain reaction. Results: in-silico constructed network revealed six mRNAs (YAP1, FOXA2, AMOTL2, TEAD2, SMAD4 and NF2), two miRNAs (miR-650 and miR-1205), and two lncRNAs (RPARP-AS1 and SRD5A3-AS1) that play important roles as a co-regulatory network in NAFLD pathogenesis. Moreover, the expression level of these constructed network–players was significantly different between NAFLD and normal control. Conclusion and future perspectives: this study provides new insight into the molecular mechanism of NAFLD pathogenesis and valuable clues for the potential use of the constructed RNA network in effective diagnostic or management strategies of NAFLD.
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Cho, Oyeon, Do-Wan Kim, and Jae-Youn Cheong. "Screening Plasma Exosomal RNAs as Diagnostic Markers for Cervical Cancer: An Analysis of Patients Who Underwent Primary Chemoradiotherapy." Biomolecules 11, no. 11 (November 14, 2021): 1691. http://dx.doi.org/10.3390/biom11111691.
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This preliminary study aimed to screen non-coding RNAs (ncRNAs) from plasma exosomes as a new method for cervical cancer diagnosis. Differentially expressed RNAs were initially selected from among a group of 12 healthy individuals (normal group) and a pretreatment group of 30 patients with cervical cancer (cancer group). Then, we analyzed the association between an ncRNA-mRNA network and cancer using ingenuity pathway analysis after secondary selection according to the number and correlation of mRNAs (or ncRNAs) relative to changes in the expression of primarily selected ncRNAs (or mRNAs) before and after chemoradiotherapy. The number of RNAs selected from the initial RNAs was one from 13 miRNAs, four from 42 piRNAs, four from 28 lncRNAs, nine from 18 snoRNAs, 10 from 76 snRNAs, nine from 474 tRNAs, nine from 64 yRNAs, and five from 67 mRNAs. The combination of miRNA (miR-142-3p), mRNAs (CXCL5, KIF2A, RGS18, APL6IP5, and DAPP1), and snoRNAs (SNORD17, SCARNA12, SNORA6, SNORA12, SCRNA1, SNORD97, SNORD62, and SNORD38A) clearly distinguished the normal samples from the cancer group samples. We present a method for efficiently screening eight classes of RNAs isolated from exosomes for cervical cancer diagnosis using mRNAs (or ncRNAs) altered by chemoradiotherapy.
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Razmara, Ehsan, Amirreza Bitaraf, Hassan Yousefi, Tina H. Nguyen, Masoud Garshasbi, William Chi-shing Cho, and Sadegh Babashah. "Non-Coding RNAs in Cartilage Development: An Updated Review." International Journal of Molecular Sciences 20, no. 18 (September 11, 2019): 4475. http://dx.doi.org/10.3390/ijms20184475.
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In the development of the skeleton, the long bones are arising from the process of endochondral ossification (EO) in which cartilage is replaced by bone. This complex process is regulated by various factors including genetic, epigenetic, and environmental elements. It is recognized that DNA methylation, higher-order chromatin structure, and post-translational modifications of histones regulate the EO. With emerging understanding, non-coding RNAs (ncRNAs) have been identified as another mode of EO regulation, which is consist of microRNAs (miRNAs or miRs) and long non-coding RNAs (lncRNAs). There is expanding experimental evidence to unlock the role of ncRNAs in the differentiation of cartilage cells, as well as the pathogenesis of several skeletal disorders including osteoarthritis. Cutting-edge technologies such as epigenome-wide association studies have been employed to reveal disease-specific patterns regarding ncRNAs. This opens a new avenue of our understanding of skeletal cell biology, and may also identify potential epigenetic-based biomarkers. In this review, we provide an updated overview of recent advances in the role of ncRNAs especially focus on miRNA and lncRNA in the development of bone from cartilage, as well as their roles in skeletal pathophysiology.
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Chen, Zhitao, Xin Lin, Zhenmiao Wan, Min Xiao, Chenchen Ding, Pengxia Wan, Qiyong Li, and Shusen Zheng. "High Expression of EZH2 Mediated by ncRNAs Correlates with Poor Prognosis and Tumor Immune Infiltration of Hepatocellular Carcinoma." Genes 13, no. 5 (May 13, 2022): 876. http://dx.doi.org/10.3390/genes13050876.
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Background: Hepatocellular carcinoma (HCC) is the predominant form of liver cancer and is accompanied by a complex regulatory network. Increasing evidence suggests that an abnormal gene expression of EZH2 is associated with HCC progression. However, the molecular mechanism by which non-coding RNAs (ncRNAs) regulate EZH2 remains elusive. Methods: The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data were used to perform differential expression analysis and prognostic analysis. We used the Encyclopedia of RNA Interactomes (ENCORI) database to predict candidate miRNAs and lncRNAs that may bind to EZH2. Subsequently, the comprehensive analysis (including expression analysis, correlation analysis, and survival analysis) identified ncRNAs that contribute to EZH2 overexpression. Results: EZH2 was found to be upregulated in the majority of tumor types and associated with a poor prognosis. Hsa-miR-101-3p was identified as a target miRNA of EZH2. Additionally, SNHG6 and MALAT1 were identified as upstream lncRNAs of hsa-miR-101-3p. Meanwhile, correlation analysis revealed that EZH2 expression was significantly associated with the infiltration of several immune cell types in HCC. Conclusion: SNHG6 or MALAT1/hsa-miR-101-3p/EZH2 axis were identified as potential regulatory pathways in the progression of HCC.
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Slaby, Ondrej, Richard Laga, and Ondrej Sedlacek. "Therapeutic targeting of non-coding RNAs in cancer." Biochemical Journal 474, no. 24 (December 14, 2017): 4219–51. http://dx.doi.org/10.1042/bcj20170079.
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The majority of the human genome encodes RNAs that do not code for proteins. These non-coding RNAs (ncRNAs) affect normal expression of the genes, including oncogenes and tumour suppressive genes, which make them a new class of targets for drug development in cancer. Although microRNAs (miRNAs) are the most studied regulatory ncRNAs to date, and miRNA-targeted therapeutics have already reached clinical development, including the mimics of the tumour suppressive miRNAs miR-34 and miR-16, which reached phase I clinical trials for the treatment of liver cancer and mesothelioma, the importance of long non-coding RNAs (lncRNAs) is increasingly being recognised. Here, we describe obstacles and advances in the development of ncRNA therapeutics and provide the comprehensive overview of the ncRNA chemistry and delivery technologies. Furthermore, we summarise recent knowledge on the biological functions of miRNAs and their involvement in carcinogenesis, and discuss the strategies of their therapeutic manipulation in cancer. We review also the emerging insights into the role of lncRNAs and their potential as targets for novel treatment paradigms. Finally, we provide the up-to-date summary of clinical trials involving miRNAs and future directions in the development of ncRNA therapeutics.
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Varì, Rosaria, Beatrice Scazzocchio, Tiziana Filardi, Anna Citarella, Maria Bellenghi, Roberta Masella, and Carmela Santangelo. "Significance of Sex Differences in ncRNAs Expression and Function in Pregnancy and Related Complications." Biomedicines 9, no. 11 (October 20, 2021): 1509. http://dx.doi.org/10.3390/biomedicines9111509.
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In the era of personalized medicine, fetal sex-specific research is of utmost importance for comprehending the mechanisms governing pregnancy and pregnancy-related complications. In recent times, noncoding RNAs (ncRNAs) have gained increasing attention as critical players in gene regulation and disease pathogenesis, and as candidate biomarkers in human diseases as well. Different types of ncRNAs, including microRNAs (miRNAs), piwi-interacting RNAs (piRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), participate in every step of pregnancy progression, although studies taking into consideration fetal sex as a central variable are still limited. To date, most of the available data have been obtained investigating sex-specific placental miRNA expression. Several studies revealed that miRNAs regulate the (patho)-physiological processes in a sexually dimorphic manner, ensuring normal fetal development, successful pregnancy, and susceptibility to diseases. Moreover, the observation that ncRNA profiles differ according to cells, tissues, and developmental stages of pregnancy, along with the complex interactions among different types of ncRNAs in regulating gene expression, strongly indicates that more studies are needed to understand the role of sex-specific ncRNA in pregnancy and associated disorders.
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Zhao, Jing, Yan Fu, Jing Wu, Juan Li, Guangjian Huang, and Lunxiu Qin. "The Diverse Mechanisms of miRNAs and lncRNAs in the Maintenance of Liver Cancer Stem Cells." BioMed Research International 2018 (2018): 1–9. http://dx.doi.org/10.1155/2018/8686027.
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Liver cancer is the second leading cause of cancer-related death worldwide. The high frequency of recurrence and metastasis is the main reason for poor prognosis. Liver cancer stem cells (CSCs) have unlimited self-renewal, differentiation, and tumor-regenerating capacities. The maintenance of CSCs may account for the refractory features of liver cancer. Despite extensive investigations, the underlying regulatory mechanisms of liver CSCs remain elusive. miRNA and lncRNA, two major classes of the ncRNA family, can exert important roles in various biological processes, and their diverse regulatory mechanisms in CSC maintenance have acquired increasing attention. However, to the best of our knowledge, there is a lack of reviews summarizing these findings. Therefore, we systematically recapitulated the latest studies on miRNAs and lncRNAs in sustaining liver CSCs. Moreover, we highlighted the potential clinical application of these dysregulated ncRNAs as novel diagnostic and prognostic biomarkers and therapeutic targets. This review not only sheds new light to fully understand liver CSCs but also provides valuable clues on targeting ncRNAs to block or eradicate CSCs in cancer treatment.