• Title/Summary/Keyword: Small regulatory RNAs

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MicroRNAs in Human Diseases: From Autoimmune Diseases to Skin, Psychiatric and Neurodegenerative Diseases

  • Ha, Tai-You
    • IMMUNE NETWORK
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    • v.11 no.5
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    • pp.227-244
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    • 2011
  • MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their target messenger RNAs (mRNAs). Recent studies have clearly demonstrated that miRNAs play critical roles in several biologic processes, including cell cycle, differentiation, cell development, cell growth, and apoptosis and that miRNAs are highly expressed in regulatory T (Treg) cells and a wide range of miRNAs are involved in the regulation of immunity and in the prevention of autoimmunity. It has been increasingly reported that miRNAs are associated with various human diseases like autoimmune disease, skin disease, neurological disease and psychiatric disease. Recently, the identification of miRNAs in skin has added a new dimension in the regulatory network and attracted significant interest in this novel layer of gene regulation. Although miRNA research in the field of dermatology is still relatively new, miRNAs have been the subject of much dermatological interest in skin morphogenesis and in regulating angiogenesis. In addition, miRNAs are moving rapidly center stage as key regulators of neuronal development and function in addition to important contributions to neurodegenerative disorder. Moreover, there is now compelling evidence that dysregulation of miRNA networks is implicated in the development and onset of human neruodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, Down syndrome, depression and schizophrenia. In this review, I briefly summarize the current studies about the roles of miRNAs in various autoimmune diseases, skin diseases, psychoneurological disorders and mental stress.

The Role of MicroRNAs in Regulatory T Cells and in the Immune Response

  • Ha, Tai-You
    • IMMUNE NETWORK
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    • v.11 no.1
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    • pp.11-41
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    • 2011
  • The discovery of microRNA (miRNA) is one of the major scientific breakthroughs in recent years and has revolutionized current cell biology and medical science. miRNAs are small (19~25nt) noncoding RNA molecules that post-transcriptionally regulate gene expression by targeting the 3' untranslated region (3'UTR) of specific messenger RNAs (mRNAs) for degradation of translation repression. Genetic ablation of the miRNA machinery, as well as loss or degradation of certain individual miRNAs, severely compromises immune development and response, and can lead to immune disorders. Several sophisticated regulatory mechanisms are used to maintain immune homeostasis. Regulatory T (Treg) cells are essential for maintaining peripheral tolerance, preventing autoimmune diseases and limiting chronic inflammatory diseases. Recent publications have provided compelling evidence that miRNAs are highly expressed in Treg cells, that the expression of Foxp3 is controlled by miRNAs and that a range of miRNAs are involved in the regulation of immunity. A large number of studies have reported links between alterations of miRNA homeostasis and pathological conditions such as cancer, cardiovascular disease and diabetes, as well as psychiatric and neurological diseases. Although it is still unclear how miRNA controls Treg cell development and function, recent studies certainly indicate that this topic will be the subject of further research. The specific circulating miRNA species may also be useful for the diagnosis, classification, prognosis of diseases and prediction of the therapeutic response. An explosive literature has focussed on the role of miRNA. In this review, I briefly summarize the current studies about the role of miRNAs in Treg cells and in the regulation of the innate and adaptive immune response. I also review the explosive current studies about clinical application of miRNA.

Incredible RNA: Dual Functions of Coding and Noncoding

  • Nam, Jin-Wu;Choi, Seo-Won;You, Bo-Hyun
    • Molecules and Cells
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    • v.39 no.5
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    • pp.367-374
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    • 2016
  • Since the RNA world hypothesis was proposed, a large number of regulatory noncoding RNAs (ncRNAs) have been identified in many species, ranging from microorganisms to mammals. During the characterization of these newly discovered RNAs, RNAs having both coding and noncoding functions were discovered, and these were considered bifunctional RNAs. The recent use of computational and high-throughput experimental approaches has revealed increasing evidence of various sources of bifunctional RNAs, such as protein-coding mRNAs with a noncoding isoform and long ncRNAs bearing a small open reading frame. Therefore, the genomic diversity of Janusfaced RNA molecules that have dual characteristics of coding and noncoding indicates that the functional roles of RNAs have to be revisited in cells on a genome-wide scale. Such studies would allow us to further understand the complex gene-regulatory network in cells. In this review, we discuss three major genomic sources of bifunctional RNAs and present a handful of examples of bifunctional RNA along with their functional roles.

Small RNA biology is systems biology

  • Jost, Daniel;Nowojewski, Andrzej;Levine, Erel
    • BMB Reports
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    • v.44 no.1
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    • pp.11-21
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    • 2011
  • During the last decade small regulatory RNA (srRNA) emerged as central players in the regulation of gene expression in all kingdoms of life. Multiple pathways for srRNA biogenesis and diverse mechanisms of gene regulation may indicate that srRNA regulation evolved independently multiple times. However, small RNA pathways share numerous properties, including the ability of a single srRNA to regulate multiple targets. Some of the mechanisms of gene regulation by srRNAs have significant effect on the abundance of free srRNAs that are ready to interact with new targets. This results in indirect interactions among seemingly unrelated genes, as well as in a crosstalk between different srRNA pathways. Here we briefly review and compare the major srRNA pathways, and argue that the impact of srRNA is always at the system level. We demonstrate how a simple mathematical model can ease the discussion of governing principles. To demonstrate these points we review a few examples from bacteria and animals.

MicroRNAs regulate granulosa cells apoptosis and follicular development - A review

  • Gong, Zhuandi;Yang, Juan;Bai, Shengju;Wei, Suocheng
    • Asian-Australasian Journal of Animal Sciences
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    • v.33 no.11
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    • pp.1714-1724
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    • 2020
  • Objective: MicroRNAs (miRNAs) are the most abundant small RNAs. Approximately 2,000 annotated miRNAs genes have been found to be differentially expressed in ovarian follicles during the follicular development (FD). Many miRNAs exert their regulatory effects on the apoptosis of follicular granulosa cells (FGCs) and FD. However, accurate roles and mechanism of miRNAs regulating apoptosis of FGCs remain undetermined. Methods: In this review, we summarized the regulatory role of each miRNA or miRNA cluster on FGCs apoptosis and FD on the bases of 41 academic articles retrieved from PubMed and web of science and other databases. Results: Total of 30 miRNAs and 4 miRNAs clusters in 41 articles were reviewed and summarized in the present article. Twenty nine documents indicated explicitly that 24 miRNAs and miRNAs clusters in 29 articles promoted or induced FGCs apoptosis through their distinctive target genes. The remaining 10 miRNAs and miRNAs of 12 articles inhibited FGCs apoptosis. MiRNAs exerted modulation actions by at least 77 signal pathways during FGCs apoptosis and FD. Conclusion: We concluded that miRNAs or miRNAs clusters could modulate the apoptosis of GCs (including follicular GCs, mural GCs and cumulus cells) by targeting their specific genes. A great majority of miRNAs show a promoting role on apoptosis of FGCs in mammals. But the accurate mechanism of miRNAs and miRNA clusters has not been well understood. It is necessary to ascertain clearly the role and mechanism of each miRNA or miRNA cluster in the future. Understanding precise functions and mechanisms of miRNAs in FGCs apoptosis and FD will be beneficial in developing new diagnostic and treatment strategies for treating infertility and ovarian diseases in humans and animals.

Roles of Oncogenic Long Non-coding RNAs in Cancer Development

  • Do, Hyunhee;Kim, Wanyeon
    • Genomics & Informatics
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    • v.16 no.4
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    • pp.18.1-18.9
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    • 2018
  • Long non-coding RNAs (lncRNAs) are classified as RNAs that are longer than 200 nucleotides and cannot be translated into protein. Several studies have demonstrated that lncRNAs are directly or indirectly involved in a variety of biological processes and in the regulation of gene expression. In addition, lncRNAs have important roles in many diseases including cancer. It has been shown that abnormal expression of lncRNAs is observed in several human solid tumors. Several studies have shown that many lncRNAs can function as oncogenes in cancer development through the induction of cell cycle progression, cell proliferation and invasion, anti-apoptosis, and metastasis. Oncogenic lncRNAs have the potential to become promising biomarkers and might be potent prognostic targets in cancer therapy. However, the biological and molecular mechanisms of lncRNA involvement in tumorigenesis have not yet been fully elucidated. This review summarizes studies on the regulatory and functional roles of oncogenic lncRNAs in the development and progression of various types of cancer.

sRNA EsrE Is Transcriptionally Regulated by the Ferric Uptake Regulator Fur in Escherichia coli

  • Hou, Bingbing;Yang, Xichen;Xia, Hui;Wu, Haizhen;Ye, Jiang;Zhang, Huizhan
    • Journal of Microbiology and Biotechnology
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    • v.30 no.1
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    • pp.127-135
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    • 2020
  • Small RNAs (sRNAs) are widespread and play major roles in regulation circuits in bacteria. Previously, we have demonstrated that transcription of esrE is under the control of its own promoter. However, the regulatory elements involved in EsrE sRNA expression are still unknown. In this study, we found that different cis-regulatory elements exist in the promoter region of esrE. We then screened and analyzed seven potential corresponding trans-regulatory elements by using pull-down assays based on DNA affinity chromatography. Among these candidate regulators, we investigated the relationship between the ferric uptake regulator (Fur) and the EsrE sRNA. Electrophoresis mobility shift assays (EMSAs) and β-galactosidase activity assays demonstrated that Fur can bind to the promoter region of esrE, and positively regulate EsrE sRNA expression in the presence of Fe2+.

MiRNA Synergistic Network Construction and Enrichment Analysis for Common Target Genes in Small-cell Lung Cancer

  • Zhang, Tie-Feng;Cheng, Ke-Wen;Shi, Wei-Yin;Zhang, Jin-Tao;Liu, Ke-Di;Xu, Shu-Guang;Chen, Ji-Quan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6375-6378
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    • 2012
  • Background: Small-cell lung cancer (also known as SCLC) is an aggressive form and untreated patients generally die within about 3 months. To obtain further insight into mechanism underlying malignancy with this cancer, an miRNA synergistic regulatory network was constructed and analyzed in the present study. Method: A miRNA microarray dataset was downloaded from the NCBI GEO database (GSE27435). A total of 546 miRNAs were identified to be expressed in SCLC cells. Then a miRNA synergistic network was constructed, and the included miRNAs mapped to the network. Topology analysis was also performed to analyze the properties of the synergistic network. Consequently, we could identified constitutive modules. Further, common target genes of each module were identified with CFinder. Finally, enrichment analysis was performed for target genes. Results: In this study, a miRNA synergistic network with 464 miRNAs and 2981 edges was constructed. According to the topology analysis, the topological properties between the networks constructed by LC related miRNAs and LC unrelated miRNAs were significantly different. Moreover, a module cilque0 could be identified in our network using CFinder. The module included three miRNAs (hsa-let-7c, hsa-let-7b and hsa-let-7d). In addition, several genes were found which were predicted to be common targets of cilque0. The enrichment analysis demonstrated that these target genes were enriched in MAPK signaling pathways. Conclusions: Although limitations exist in the current data, the results uncovered here are important for understanding the key roles of miRNAs in SCLC. However, further validation is required since our results were based on microarray data derived from a small sample size.

Therapeutic implications of microRNAs in pulmonary arterial hypertension

  • Lee, Aram;McLean, Danielle;Choi, Jihea;Kang, Hyesoo;Chang, Woochul;Kim, Jongmin
    • BMB Reports
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    • v.47 no.6
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    • pp.311-317
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    • 2014
  • microRNAs (miRNAs) are a class of small, non-coding RNAs that play critical posttranscriptional regulatory roles typically through targeting of the 3'-untranslated region of messenger RNA (mRNA). Mature miRNAs are known to be involved in global cellular processes, such as differentiation, proliferation, apoptosis, and organogenesis, due to their capacity to target multiple mRNAs. Thus, imbalances in the expression and/or activity of miRNAs are involved in the pathogenesis of numerous diseases, including pulmonary arterial hypertension (PAH). PAH is a progressive disease characterized by vascular remodeling due to excessive proliferation of pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs). Recently, studies have evaluated the roles of miRNAs involved in the pathogenesis of PAH in these pulmonary vascular cells. This review provides an overview of recent discoveries on the role of miRNAs in the pathogenesis of PAH and discusses the potential for miRNAs as therapeutic targets and biomarkers of PAH.

microRNA-29b: an Emerging Player in Human Cancer

  • Liu, Hao;Wang, Bin;Lin, Jie;Zhao, Liang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9059-9064
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    • 2014
  • MicroRNAs (miRNAs) are ubiquitously expressed small, non-coding RNAs that negatively regulate gene expression at a post transcriptional/translational level. They have emerging as playing crucial roles in cancer at all stages ranging from initiation to metastasis. As a tumor suppressor miRNA, aberrant expression of microRNA-29b (miR-29b) has been detected in various types of cancer, and its disturbance is related with tumor development and progression. In this review, we summarize the latest findings with regard to the tumor suppressor signatureof miR-29b and its regulatory mechanisms. Our review highlights the diverse relationships between miR-29b and its target genes in malignant tumors.