An unbiased silencing screen in muscle cells identifies miR-320a, miR-150, miR-196b, and miR-34c as regulators of skeletal muscle mitochondrial metabolism

Objective: Strategies improving skeletal muscle mitochondrial capacity are commonly paralleled by improvements in (metabolic) health. We and others previously identified microRNAs regulating mitochondrial oxidative capacity, but data in skeletal muscle are limited. Therefore, the present study aimed...

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Main Authors: Dennis Dahlmans (Author), Alexandre Houzelle (Author), Pénélope Andreux (Author), Johanna A. Jörgensen (Author), Xu Wang (Author), Leon J. de Windt (Author), Patrick Schrauwen (Author), Johan Auwerx (Author), Joris Hoeks (Author)
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Published: Elsevier, 2017-11-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Dennis Dahlmans  |e author 
700 1 0 |a Alexandre Houzelle  |e author 
700 1 0 |a Pénélope Andreux  |e author 
700 1 0 |a Johanna A. Jörgensen  |e author 
700 1 0 |a Xu Wang  |e author 
700 1 0 |a Leon J. de Windt  |e author 
700 1 0 |a Patrick Schrauwen  |e author 
700 1 0 |a Johan Auwerx  |e author 
700 1 0 |a Joris Hoeks  |e author 
245 0 0 |a An unbiased silencing screen in muscle cells identifies miR-320a, miR-150, miR-196b, and miR-34c as regulators of skeletal muscle mitochondrial metabolism 
260 |b Elsevier,   |c 2017-11-01T00:00:00Z. 
500 |a 2212-8778 
500 |a 10.1016/j.molmet.2017.08.007 
520 |a Objective: Strategies improving skeletal muscle mitochondrial capacity are commonly paralleled by improvements in (metabolic) health. We and others previously identified microRNAs regulating mitochondrial oxidative capacity, but data in skeletal muscle are limited. Therefore, the present study aimed to identify novel microRNAs regulating skeletal muscle mitochondrial metabolism. Methods and results: We conducted an unbiased, hypothesis-free microRNA silencing screen in C2C12 myoblasts, using >700 specific microRNA inhibitors, and investigated a broad panel of mitochondrial markers. After subsequent validation in differentiated C2C12 myotubes, and exclusion of microRNAs without a human homologue or with an adverse effect on mitochondrial metabolism, 19 candidate microRNAs remained. Human clinical relevance of these microRNAs was investigated by measuring their expression in human skeletal muscle of subject groups displaying large variation in skeletal muscle mitochondrial capacity. Conclusion: The results show that that microRNA-320a, microRNA-196b-3p, microRNA-150-5p, and microRNA-34c-3p are tightly related to in vivo skeletal muscle mitochondrial function in humans and identify these microRNAs as targets for improving mitochondrial metabolism. 
546 |a EN 
690 |a Skeletal muscle metabolism 
690 |a Mitochondria 
690 |a MicroRNA 
690 |a Screening 
690 |a Type 2 diabetes 
690 |a Oxidative capacity 
690 |a Internal medicine 
690 |a RC31-1245 
655 7 |a article  |2 local 
786 0 |n Molecular Metabolism, Vol 6, Iss 11, Pp 1429-1442 (2017) 
787 0 |n http://www.sciencedirect.com/science/article/pii/S2212877817303125 
787 0 |n https://doaj.org/toc/2212-8778 
856 4 1 |u https://doaj.org/article/d32d600aa61b4cec93b38bbde9c340f4  |z Connect to this object online.