Small EM, Olson EN. Pervasive roles of microRNAs in cardiovascular biology. Nature 2011; 469: 336-342

Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9148, USA.
Nature (Impact Factor: 41.46). 01/2011; 469(7330):336-42. DOI: 10.1038/nature09783
Source: PubMed


First recognized as regulators of development in worms and fruitflies, microRNAs are emerging as pivotal modulators of mammalian cardiovascular development and disease. Individual microRNAs modulate the expression of collections of messenger RNA targets that often have related functions, thereby governing complex biological processes. The wideranging functions of microRNAs in the cardiovascular system have provided new perspectives on disease mechanisms and have revealed intriguing therapeutic targets, as well as diagnostics, for a variety of cardiovascular disorders.

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    • "Unlike transcriptional factor-mediated regulation of gene expression, which appears to be " on or off, " miRNAs tend to only moderately regulate the overall level of their target's expression, so they are referred to as " fine-tuners " [21]. Although the effect of a single miRNA on a specific gene may appear to be small, the combinatory effect of miRNAs on multiple mRNA targets functioning within the same biological pathway can be synergistic and sometimes dramatic [22] [23]. In addition, a mRNA normally possesses multiple miRNA-binding sites in its 3 í® í° UTR and is likely a target for numerous different miRNAs. "
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    ABSTRACT: A healthy and independent life requires skeletal muscles to maintain optimal function throughout the lifespan, which is in turn dependent on efficient activation of processes that regulate muscle development, homeostasis, and metabolism. Thus, identifying mechanisms that modulate these processes is of crucial priority. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), have emerged as a class of previously unrecognized transcripts whose importance in a wide range of biological processes and human disease is only starting to be appreciated. In this review, we summarize the roles of recently identified miRNAs and lncRNAs during skeletal muscle development and pathophysiology. We also discuss several molecular mechanisms of these noncoding RNAs. Undoubtedly, further systematic understanding of these noncoding RNAs' functions and mechanisms will not only greatly expand our knowledge of basic skeletal muscle biology, but also significantly facilitate the development of therapies for various muscle diseases, such as muscular dystrophies, cachexia, and sarcopenia.
    08/2015; 2015(2):676575. DOI:10.1155/2015/676575
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    • "MicroRNAs (miRNAs) are short 18–24 nucleotide, singlestranded , noncoding RNAs that bind to the complementary target sites in 3 í® í° -untranslated regions (3 í® í° -UTRs) of specific mRNA targets to inhibit translation or to cause mRNA degradation [1]. It is estimated that the human genome contains more than 1,000 miRNAs, which regulate at least 30% of protein-coding genes [2] [3] [4]. In addition, one single miRNA can exert inhibitory effects on many mRNAs, whereas one single mRNA can be modulated by many miRNAs. "
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    ABSTRACT: MicroRNAs (miRNAs) play an essential role in the onset and development of many cardiovascular diseases. Increasing evidence shows that miRNAs can be used as potential diagnostic biomarkers for cardiovascular diseases, and miRNA-based therapy may be a promising therapy for the treatment of cardiovascular diseases. The microRNA-143/-145 (miR-143/-145) cluster is essential for differentiation of vascular smooth muscle cells (VSMCs) and determines VSMC phenotypic switching. In this review, we summarize the recent progress in knowledge concerning the function of miR-143/-145 in the cardiovascular system and their role in cardiovascular diseases. We discuss the potential role of miR-143/-145 as valuable biomarkers for cardiovascular diseases and explore the potential strategy of targeting miR-143 and miR-145.
    07/2015; 2015(38):531740. DOI:10.1155/2015/531740
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    • "For underscoring the therapeutic potential of miRNAs in cardiovascular diseases, the overexpression or downregulation of a single miRNA is enough to cause the pathological alteration [Pan et al., 2010]. Endogenously-made miRNAs (~22 nt) act by binding to the complementary sequences of their target transcripts, resulting in translational repression or mRNA degradation [Small and Olson, 2011]. As miRNAs could provide a new mean to manipulate stem and progenitor cells fate, understanding their pattern of expression and their roles during the cardiac differentiation is of crucial importance [Srivastava , 2006; Cordes and Srivastava, 2009]. "
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    ABSTRACT: Background The cardiac cells generation via stem cells differentiation is a promising approach to restore the myocardial infarction. Promoted by our primary bioinformatics analysis as well as some previously published data on potential role of hsa-miR-590-3p in cardiogenesis, we have tried to decipher the role of miR-590-5p during the course of differentiation of cardiosphere-derived cells (CDCs).Methods The differentiation induction of CDCs by TGFB1 was confirmed by real-time PCR, ICC and flow cytometry. The expression pattern of hsa-miR-590-5p and some related genes were examined during the differentiation process. In order to study the role of miR- 590-5p in cardiac differentiation, the effect of miR-590 overexpression in CDCs was studied.ResultsEvaluating the expression patterns of miR-590 and its potential targets (TGFBRs) during the course of differentiation, demonstrated a significant downregulation of miR-590 and an upregulation of TGFBR2, following the treatment of CDCs with TGFB1. Therefore, we proposed a model in which TGFB1 exerts its differentiation induction via downregulation of miR-590, and hence the higher transcriptional expression level of TGFBR2. In accordance with our proposed model, transfection of CDCs by a pLenti-III-hsa-mir-590-GFP expression vector before or after the first TGFB1 treatment caused a significant alteration in the expression levels of TGFBRs. Moreover, our data revealed that overexpression of miR-590 before TGFB1 induction was able to attenuate the CDCs differentiation probably via the reduction of TGFBR2 expression level.Conclusions Altogether, our data suggest an inhibitory role of miR-590 during the cardiac differentiation of CDCs which its suppression might elevate the rate of differentiation. J. Cell. Biochem. © 2014 Wiley Periodicals, Inc.
    Journal of Cellular Biochemistry 01/2015; 116(1). DOI:10.1002/jcb.24957 · 3.26 Impact Factor
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