MicroRNAs Are Aberrantly Expressed in Hypertrophic Heart : Do They Play a Role in Cardiac Hypertrophy?
Yunhui Cheng,Ruirui Ji,Junming Yue,Jian Yang,Xiaojun Liu,He Chen,David B. Dean,Chunxiang Zhang +7 more
TLDR
It is demonstrated that miRNAs are aberrantly expressed in hypertrophic mouse hearts, and modulating miR-21 expression via antisense-mediated depletion (knockdown) had a significant negative effect on cardiomyocyte hypertrophy.Abstract:
MicroRNAs (miRNAs) are a recently discovered class of endogenous, small, noncoding RNAs that regulate gene expression. Although miRNAs are highly expressed in the heart, their roles in heart diseases are currently unclear. Using microarray analysis designed to detect the majority of mammalian miRNAs identified thus far, we demonstrated that miRNAs are aberrantly expressed in hypertrophic mouse hearts. The time course of the aberrant miRNA expression was further identified in mouse hearts at 7, 14, and 21 days after aortic banding. Nineteen of the most significantly dysregulated miRNAs were further confirmed by Northern blot and/or real-time polymerase chain reaction, in which miR-21 was striking because of its more than fourfold increase when compared with the sham surgical group. Similar aberrant expression of the most up-regulated miRNA, miR-21, was also found in cultured neonatal hypertrophic cardiomyocytes stimulated by angiotensin II or phenylephrine. Modulating miR-21 expression via antisense-mediated depletion (knockdown) had a significant negative effect on cardiomyocyte hypertrophy. The results suggest that miRNAs are involved in cardiac hypertrophy formation. miRNAs might be a new therapeutic target for cardiovascular diseases involving cardiac hypertrophy such as hypertension, ischemic heart disease, valvular diseases, and endocrine disorders.read more
Citations
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MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts
Thomas Thum,Carina Gross,Jan Fiedler,Thomas Fischer,Stephan Kissler,Markus Bussen,Paolo Galuppo,Steffen Just,Wolfgang Rottbauer,Stefan Frantz,Mirco Castoldi,Jürgen Soutschek,Victor Koteliansky,Andreas Rosenwald,M. Albert Basson,Jonathan D. Licht,John T. R. Pena,Sara H. Rouhanifard,Martina U. Muckenthaler,Thomas Tuschl,Gail R. Martin,Johann Bauersachs,Stefan Engelhardt,Stefan Engelhardt +23 more
TL;DR: It is shown that microRNA-21 regulates the ERK–MAP kinase signalling pathway in cardiac fibroblasts, which has impacts on global cardiac structure and function and confirms miR-21 as a disease target in heart failure and establishes the therapeutic efficacy of microRNA therapeutic intervention in a cardiovascular disease setting.
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Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis
Eva van Rooij,Lillian B. Sutherland,Jeffrey E. Thatcher,J. Michael DiMaio,R. Haris Naseem,William S. Marshall,Joseph A. Hill,Eric N. Olson +7 more
TL;DR: It is concluded that miR-29 acts as a regulator of cardiac fibrosis and represents a potential therapeutic target for tissue fibrosis in general.
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Small non-coding RNAs in animal development
Giovanni Stefani,Frank J. Slack +1 more
TL;DR: Improved understanding of the biological functions of small non-coding RNAs has been fostered by the analysis of genetic deletions of individual miRNAs in mammals, and studies show that miRNA are key regulators of animal development and are potential human disease loci.
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MicroRNAs in development and disease.
Danish Sayed,Maha Abdellatif +1 more
TL;DR: The discovery, structure, and mode of function of miRNAs in mammalian cells are described, before elaborating on their roles and significance during development and pathogenesis in the various mammalian organs, while attempting to reconcile their functions with the existing knowledge of their targets.
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miR‐21: a small multi‐faceted RNA
TL;DR: The aim of this study was to identify miR‐21 as a diagnostic and prognostic marker and potential therapeutic target for gliomas and investigate the mechanisms of elevation in cancer.
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