Regulatory Roles of MicroRNAs in Diabetes

Feng, Juan; Xing, Wanli; Xie, Liang

doi:10.3390/ijms17101729

Cited by 122 publications

(99 citation statements)

References 68 publications

(70 reference statements)

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“…Dysregulation of miRNAs and their effect on the target genes has been also shown in metabolic disorders [5]. Some miRNAs are known for their potential therapeutic functions [6].…”

Section: Introductionmentioning

confidence: 99%

Expression of the miR-302/367 microRNA cluster is regulated by a conserved long non-coding host gene

Rahimi

Füchtbauer

Fathi

et al. 2018

Preprint

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MicroRNAs (miRNAs) are important regulators of cellular functions. MiR-302/367 is a polycistronic miRNA cluster including miR-302b/c/a/d (collectively termed miR-302s) and miR-367. The cluster is located in the intron of a non-coding host gene. MiR-302s have been shown to repress mRNAs required for differentiation and to induce pluripotency in somatic cells. The stem cell specific transcription factors OCT4, SOX2 and Nanog drive miR-302s expression, however, the reported expression in human and mice indicates a more complex transcriptional regulation. Here we investigate the transcriptional control and the processing of the miR-302 host gene. The murine miR-302 host gene is alternatively spliced, polyadenylated and exported from the nucleus. The regulatory sequences extend at least 2 kb upstream of the transcription start side and contain several conserved binding sites for both transcriptional activators and repressors. Reporter constructs with different upstream regions revealed a significant influence of the more distant regulatory sequences in pluripotent stem cells. The gene structure and regulatory elements like binding sites for activating and repressing transcriptional regulators, splice, and polyadenylation signals are highly conserved between mouse and human. So far, no miR-302 independent function has been annotated for the miR-302 host gene and we hypothesize that the complex and differential regulation of the miRNA transcription and processing might the reason for its conservation. Thus, regulation or micro-RNA expression might be a so far less recognized function of non-coding RNA genes. Author SummaryNon-coding RNAs constitute a large part of the mammalian genome. Interestingly, some long non-coding RNAs (lncRNA) are transcribed and processed in the same way as mRNAs but lack an open reading frame. Here we give evidence that a so far less recognized function of such lncRNAs could be to supply microRNAs with the complex transcriptional control and processing required for their intricate expression. As an example, we analyzed the regulatory sequences of the miR-302/367 host gene. MiR-302/367 is a microRNA cluster involved in the regulation of stem cells and cellular differentiation. We show here that the regulatory region is much more complex than anticipated, a complexity that can not be conferred alone by any of the stem cell specific transcription factors which were so far associated with the expression of miR-302/367.

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“…Dysregulation of miRNAs and their effect on the target genes has been also shown in metabolic disorders [5]. Some miRNAs are known for their potential therapeutic functions [6].…”

Section: Introductionmentioning

confidence: 99%

Expression of the miR-302/367 microRNA cluster is regulated by a conserved long non-coding host gene

Rahimi

Füchtbauer

Fathi

et al. 2018

Preprint

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“…MicroRNAs (miRNAs) are small noncoding RNAs, which are considered as key regulators of gene expression at the posttranscriptional level and multiple pathophysiological processes [7,8]. Accumulated studies have strongly suggested miRNAs are essential in regulating pancreatic β cell functions, the release of insulin, and insulin resistance [9]. A number of miRNAs have been identified as promising biomarkers for the diagnosis of GDM, including miR-16-5p, miR-375, and the let-7 family [10,11].…”

Section: Introductionmentioning

confidence: 99%

miR-657 Promotes Macrophage Polarization toward M1 by Targeting FAM46C in Gestational Diabetes Mellitus

Wang

Liu

et al. 2019

Mediators of Inflammation

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MicroRNA (miRNA) has been widely suggested to play a vital role of in the pathogenesis of gestational diabetes mellitus (GDM). We have previously demonstrated that miR-657 can regulate macrophage inflammatory response in GDM. However, the role of miR-657 on M1/M2 macrophage polarization in GDM pathogenesis is not clear yet. This study is aimed at elucidating this issue and identifying novel potential GDM therapeutic targets based on miRNA network. miR-657 is found to be upregulated in placental macrophages demonstrated by real-time PCR, which can enhance macrophage proliferation and migration in vitro. Luciferase reporter assay shows the evidence that FAM46C is a target of miR-657. In addition, miR-657 can promote macrophage polarization toward the M1 phenotype by downregulating FAM46C in macrophages. The present study strongly suggests miR-657 is involved in GDM pathogenesis by regulating macrophage proliferation, migration, and polarization via targeting FAM46C. miR-657/FAM46C may serve as promising targets for GDM diagnosis and treatment.

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“…112 MicroRNAs can particularly affect pancreatic β-cells through the regulation of cell survival and apoptosis, proliferation, differentiation, or insulin secretion. 113 Besides, they are also implicated in the insulin resistance regulation by targeting insulin receptors and their substrates. 113 MicroRNAs have been also shown to be important regulators of hypertension and blood pressure.…”

Section: Other Risk Factors For Atherosclerosis and Microrna Targetingmentioning

confidence: 99%

“…113 Besides, they are also implicated in the insulin resistance regulation by targeting insulin receptors and their substrates. 113 MicroRNAs have been also shown to be important regulators of hypertension and blood pressure. Notably, a murine models of Dicer deletion displayed a drop in blood pressure, 114 as well as miR-143/-145 KO mice, 115 and plethora of microRNAs were shown to be involved in hypertension in both human studies and animal models.…”

Section: Other Risk Factors For Atherosclerosis and Microrna Targetingmentioning

confidence: 99%

MicroRNAs in the Pathobiology and Therapy of Atherosclerosis

Laffont

Rayner

2017

Canadian Journal of Cardiology

139

111

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MicroRNAs are short non-coding RNAs, expressed in humans and involved in sequence-specific post-transcriptional regulation of gene expression. They have emerged as key players in a wide array of biological processes, and changes in their expression and/or function have been associated with plethora of human diseases. Atherosclerosis and its related clinical complications, such as myocardial infarction or stroke, represent the leading cause of death in the western world. Accumulating experimental evidence has revealed a key role for microRNAs in regulating cellular and molecular processes related to atherosclerosis development, ranging from risk factors, to plaque initiation and progression, up to atherosclerotic plaque rupture. In this review, we will focus on how microRNAs can influence atherosclerosis biology, as well as the potential clinical applications of microRNAs which are being developed as both targets and therapeutics for a growing industry hoping to harness the power of RNA-guided gene regulation to fight disease and infection.

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Regulatory Roles of MicroRNAs in Diabetes

Cited by 122 publications

References 68 publications

Expression of the miR-302/367 microRNA cluster is regulated by a conserved long non-coding host gene

Expression of the miR-302/367 microRNA cluster is regulated by a conserved long non-coding host gene

miR-657 Promotes Macrophage Polarization toward M1 by Targeting FAM46C in Gestational Diabetes Mellitus

MicroRNAs in the Pathobiology and Therapy of Atherosclerosis

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