miR-29b contributes to multiple types of muscle atrophy

Li, Jin; Chan, Ming C.; Yu, Yan; Bei, Yihua; Chen, Ping; Zhou, Qing; Cheng, Liming; Chen, Lei; Ziegler, Olivia; Rowe, Glenn C.; Das, Saumya; Xiao, Junjie

doi:10.1038/ncomms15201

Cited by 184 publications

(220 citation statements)

References 50 publications

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“…For example, miR-29 was decreased after acute myocardial infarction, which targets a cadre of mRNAs encoding proteins involved in fibrosis to promote the fibrotic response [5]. This was confirmed in another report in which miR-29b was shown to target insulin-like growth factor 1 and phosphatidylinositol 3-kinase and contribute to muscle atrophy [6]. Microarray profiling also showed alterations in genes related to ion channels by comparing DCM patients with controls: sodium voltage-gated channel beta subunit 2 was increased, while potassium voltage-gated channel subfamily J member 5/8, chloride intracellular channel 2/3, and calcium voltage-gated channel auxiliary subunit B2/A1C were decreased [7].…”

Section: Introductionsupporting

confidence: 60%

Serum Exosomal MiR-92b-5p as a Potential Biomarker for Acute Heart Failure Caused by Dilated Cardiomyopathy

Chen²,

Du³

et al. 2018

Cell Physiol Biochem

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Background/Aims: MicroRNAs (miRNAs) can be used as biomarkers for cardiovascular diseases, especially for heart failure. However, there are few reports on serum exosomal miRNA biomarkers in patients with acute heart failure (AHF) due to Dilated cardiomyopathy (DCM). Methods: We analyzed 3 different serum exosomal miRNAs (exo-miR-92b-5p, exo-miR-192-5p, and exo-miR-320a) in 43 patients with DCM-AHF and 34 healthy volunteers as a control group (CG) by using exosome separation followed by a quantitative reverse-transcript PCR assay. Exosomes were identified by electron microscopy, NaNOZS-90, and western blot analyses (CD63 and Hsp70). Results: Serum exo-miR-92b-5p expression was increased in DCM-AHF patients compared to the CG (Mann–Whitney U-test: P < 0.001). Exo-miR-92b-5p was positively related to age and some ultrasound data (Spearman’s correlation: exo-miR-92b-5p vs. age, r = 0.297, P = 0.014; exo-miR-92b-5p vs. left atrial diameter, r = 0.431, P < 0.001; exo-miR-92b-5p vs. left ventricular diastolic diameter, r = 0.419, P < 0.001; exo-miR-92b-5p vs. left ventricular systolic diameter, r = 0.446, P < 0.001). Exo-miR-92b-5p was also negatively related to other ultrasound data (Spearman’s correlation: exo-miR-92b-5p vs. left ventricular fraction shortening, r = -0.497, P < 0.001; exo-miR-92b-5p vs. left ventricular ejection fraction, r = -0.482, P < 0.001). The discrimination of DCM-AHF patients from the CG by exo-miR-92b-5p was demonstrated by a receiver operating characteristic curve (exo-miR-92b-5p: cutoff value = 0.0023, area under the curve = 0.808, P < 0.001, sensitivity = 62.8%, specificity = 85.3%). Conclusion: Serum exo-miR-92b-5p is a potential biomarker for the diagnosis of DCM-AHF.

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Section: Introductionsupporting

confidence: 60%

Serum Exosomal MiR-92b-5p as a Potential Biomarker for Acute Heart Failure Caused by Dilated Cardiomyopathy

Chen²,

Du³

et al. 2018

Cell Physiol Biochem

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“…We performed a GO-term enrichment analysis of miR-29 targets with 8-mer seed matches and found that about half of the top pathways were related to ECM structure or insulin signaling, consistent with miR-29’s previously described roles in liver, cornea, muscle, and heart (Supplementary Fig. 2c) 21,22,23,24 . A closer examination of individual miR-29 targets, ranked by peak height, reveals that 4 of the top 10 genes have been previously validated in other cell types (Fig.…”

Section: Figsupporting

confidence: 81%

AGO HITS-CLIP in Adipose Tissue Reveals miR-29 as a Post-Transcriptional Regulator of Leptin

O’Connor

Murphy

et al. 2020

Preprint

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MicroRNAs (miRNAs) are short, non-coding RNAs that associate with Argonaute (AGO) to regulate mRNA stability and translation. While individual miRNAs have been shown to play important roles in white and brown adipose tissue in normal physiology and disease 1,2,3 , a comprehensive analysis of miRNA activity in these tissues has not been performed. We used high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP) to comprehensively characterize the network of high-confidence, in vivo mRNA:miRNA interactions across white and brown fat, revealing over 100,000 unique miRNA binding sites. Targets for each miRNA were ranked to generate a catalog of miRNA binding activity, and the miR-29 family emerged as a top regulator of adipose tissue gene expression. Among the top targets of miR-29 was leptin, an adipocyte-derived hormone that acts on the brain to regulate food intake and energy expenditure 4 . Two independent miR-29 binding sites in the leptin 3'-UTR were validated using luciferase assays, and miR-29 gain and loss-of-function modulated leptin mRNA and protein secretion in primary adipocytes. In mice, miR-29 abundance inversely correlated with leptin levels in two independent models of obesity. This work represents the only experimentally generated miRNA targetome in adipose tissue and identifies the first known post-transcriptional regulator of leptin. Future work aimed at manipulating miR-29:leptin binding may provide a therapeutic opportunity to treat obesity and its sequelae.Much of the work on adipocyte development and function over the last several decades has focused on transcriptional regulators. These include PPARG2, which is necessary and sufficient for the development and maintenance of white and brown adipocytes 5 , and PRDM16, which regulates brown and beige adipocyte identity 6,7 . More recently, it has become clear that post-transcriptional regulators also play 3 a key role in influencing adipocyte phenotype. Studies with adipose-specific dicer KO mice demonstrate that microRNAs (miRNAs) are essential in regulating adipogenesis, insulin sensitivity and non-shivering thermogenesis 8,9 . Several individual miRNAs have been shown to contribute to these phenotypic effects.miR-133 represses BAT function by directly targeting Prdm16 and inhibiting expression of thermogenic genes 2 . miR-196a induces browning of WAT by targeting Hoxc8 1 , and miR-26 protects mice from dietinduced obesity by blocking adipogenesis 10 . These studies, and most others in adipose tissue, rely on computational predictions and low-throughput validation to identify miRNA targets. Although highthroughput crosslinking techniques to map the miRNA targetome have been applied to liver, brain, heart and other tissues 11,12,13 , thus far, no comprehensive targetome has been described for adipose tissue.To profile the complete network of in vivo, adipose-specific miRNA binding activity across both brown and white fat, we used AGO HITS-CLIP on interscapular brown adipose tissue (iBAT) and epididymal white a...

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“…MiR-29b is the one that results in multiple types of muscle atrophy. Our research can further be applied to miR-29b (Li, et al, 2017). Furthermore, in the current models, we focus on the direct regulation between each miRNA and its target mRNA/protein, in the future, we will also take indirect regulation into consideration.…”

Section: Discussionmentioning

confidence: 99%

Integrated Identification of Disease Specific Pathways Using Multi-omics data

Chang

Hoffman

et al. 2019

Preprint

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Motivation: Identification of biological pathways plays a central role in understanding both human health and diseases. Although much work has previously been done to explore the biological pathways by using single omics data, little effort has been reported using multiomics data integration, mainly due to methodological and technological limitations. Compared to single omics data, multi-omics data will help identifying disease specific functional pathways with both higher sensitivity and specificity, thus gaining more comprehensive insights into the molecular architecture of disease processes. Results:In this paper, we propose two computational approaches that integrate multi-omics data and identify disease-specific biological pathways with high sensitivity and specificity.Applying our methods to an experimental multi-omics data dataset on muscular dystrophy subtypes, we identified disease-specific pathways of high biological plausibility. The developed methodology will likely have a broad impact on improving the molecular characterization of many common diseases. Contact: yuewang@vt.eduSupplementary information: Supplementary information attached.

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miR-29b contributes to multiple types of muscle atrophy

Cited by 184 publications

References 50 publications

Serum Exosomal MiR-92b-5p as a Potential Biomarker for Acute Heart Failure Caused by Dilated Cardiomyopathy

Serum Exosomal MiR-92b-5p as a Potential Biomarker for Acute Heart Failure Caused by Dilated Cardiomyopathy

AGO HITS-CLIP in Adipose Tissue Reveals miR-29 as a Post-Transcriptional Regulator of Leptin

Integrated Identification of Disease Specific Pathways Using Multi-omics data

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