A Novel Cardiomyocyte-enriched MicroRNA, miR-378, Targets Insulin-like Growth Factor 1 Receptor

Knezevic, Ivana; Patel, Aalok; Sundaresan, Nagalingam R.; Gupta, Mahesh P.; Solaro, R. John; Nagalingam, Raghu S.; Gupta, Madhu

doi:10.1074/jbc.m111.331751

Cited by 123 publications

(106 citation statements)

References 41 publications

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“…We found that mice lacking miR-378 and miR-378* are protected against diet-induced obesity. Previous studies have identified numerous metabolic regulatory proteins as targets for repression by miR-378 and miR-378* (10,(26)(27)(28). In addition, we found that carnitine O-acetyltransferase (CRAT), a mitochondrial enzyme involved in fatty acid metabolism (29,30), and MED13 are repressed by miR-378 and miR-378*, respectively.…”

mentioning

confidence: 65%

“…In addition, miR-378 targets the transcriptional repressor MyoR during myoblast differentiation, increasing the activity of the myogenic transcription factor MyoD, which in turn up-regulates miR-378 within a regulatory feed-forward loop (46). Furthermore, miR-378 has been reported to target the insulin-like growth factor 1 receptor and to promote apoptosis in cardiomyocytes (28).…”

Section: Discussionmentioning

confidence: 99%

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Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*

Carrer

Liu²,

Grueter

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

263

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Obesity and metabolic syndrome are associated with mitochondrial dysfunction and deranged regulation of metabolic genes. Peroxisome proliferator-activated receptor γ coactivator 1β (PGC-1β) is a transcriptional coactivator that regulates metabolism and mitochondrial biogenesis through stimulation of nuclear hormone receptors and other transcription factors. We report that the PGC-1β gene encodes two microRNAs (miRNAs), miR-378 and miR-378*, which counterbalance the metabolic actions of PGC-1β. Mice genetically lacking miR-378 and miR-378* are resistant to high-fat diet-induced obesity and exhibit enhanced mitochondrial fatty acid metabolism and elevated oxidative capacity of insulin-target tissues. Among the many targets of these miRNAs, carnitine O-acetyltransferase, a mitochondrial enzyme involved in fatty acid metabolism, and MED13, a component of the Mediator complex that controls nuclear hormone receptor activity, are repressed by miR-378 and miR-378*, respectively, and are elevated in the livers of miR-378/378* KO mice. Consistent with these targets as contributors to the metabolic actions of miR-378 and miR-378*, previous studies have implicated carnitine O-acetyltransferase and MED13 in metabolic syndrome and obesity. Our findings identify miR-378 and miR-378* as integral components of a regulatory circuit that functions under conditions of metabolic stress to control systemic energy homeostasis and the overall oxidative capacity of insulin target tissues. Thus, these miRNAs provide potential targets for pharmacologic intervention in obesity and metabolic syndrome.fatty acid oxidation | adipocytes | mitochondrial CO 2 production

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mentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*

Carrer

Liu²,

Grueter

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

263

View full text Add to dashboard Cite

show abstract

“…It was first identified in the heart as a miRNA that is expressed at significantly higher levels in 7-day-old neonatal mice compared with 16-day fetal hearts. 45 miR-378 is expressed in both cardiac and skeletal muscle and was shown to directly downregulate expression of the insulin-like growth factor receptor 1 by binding to its mRNA. In neonatal cardiomyocytes, miR-378 overexpression leads to decreased insulin-like growth factor receptor 1 and inhibition of its downstream effectors PI-3K (phosphatidylinositol 3-kinase) and Akt.…”

Section: Mir-378 Regulation Of Hypertrophic Signalingmentioning

confidence: 99%

“…In neonatal cardiomyocytes, miR-378 overexpression leads to decreased insulin-like growth factor receptor 1 and inhibition of its downstream effectors PI-3K (phosphatidylinositol 3-kinase) and Akt. 45 These are important antiapoptotic signals under conditions of stress, and in fact inhibiting miR-378 was cardioprotective against apoptosis in response to hydrogen peroxide or hypoxic stress.…”

Section: Mir-378 Regulation Of Hypertrophic Signalingmentioning

confidence: 99%

MicroRNAs in Heart Failure

Melman

Shah²,

Das³

2014

Circ: Heart Failure

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“…us in addition to its role in BMC survival, reduction in miR-34 levels also bene�ts myocytes, which are probably regulated via the release of IGF-1 by BMC and thereby improve myocyte survival [59]. IGF1 also reduced miR-378 expression in cardiomyocytes, thereby protecting cardiomyocytes from cell death by promoting IGF1R expression and downstream Akt signaling cascades, whereas overexpression of miR-378 enhanced apoptosis of cardiomyocytes [60]. is paracrine regulation of cardiac miRNAs by transplanted BMCs contributes to the protective effects of cell therapy [59].…”

Section: Mirnas In Cardiomyocyte Andmentioning

confidence: 99%

MicroRNAs in Cardiovascular Regenerative Medicine: Directing Tissue Repair and Cellular Differentiation

Sluijter

2013

ISRN Vascular Medicine

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MicroRNAs (miRNAs) are a class of short noncoding RNA molecules, approximately 22 nucleotides in length, which regulate gene expression through inhibition of the translation of target genes. It is now generally accepted that miRNAs guide processes and cellular functions through precise titration of gene dosage, not only for a single gene but also controlling the levels of a large cohort of gene products. miRNA expression is altered in cardiovascular disease and may thereby limit and impair cardiovascular repair responses. Increasing evidence of the essential role of miRNAs in the self-renewal and differentiation of stem cells suggests the opportunity of using the modulation of miRNA levels or their function in directing cell transplantation, cell behavior, and thereby organ healing. In this paper, an overview of miRNA biogenesis and their way of action and different roles that miRNAs play during the myocardial responses to injury and upon cell transplantation will be provided. We focused on cardiomyocyte survival, angiogenesis, extracellular matrix production, and how miRNAs can direct cell plasticity of injected cells and thus drive differentiation for cardiovascular phenotypes, including vascular differentiation and cardiomyocyte differentiation.

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A Novel Cardiomyocyte-enriched MicroRNA, miR-378, Targets Insulin-like Growth Factor 1 Receptor

Cited by 123 publications

References 41 publications

Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*

Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*

MicroRNAs in Heart Failure

MicroRNAs in Cardiovascular Regenerative Medicine: Directing Tissue Repair and Cellular Differentiation

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