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Mol Metab. 2017 Nov;6(11):1429-1442. doi: 10.1016/j.molmet.2017.08.007. Epub 2017 Aug 31.

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

Author information

1
Department of Human Biology and Human Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, 6200MD, The Netherlands.
2
Laboratory of Integrative Systems Physiology, École polytechnique fédérale de Lausanne, Lausanne, CH-1015, Switzerland.
3
Department of Cardiology, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, 6200MD, The Netherlands.
4
Department of Human Biology and Human Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, 6200MD, The Netherlands. Electronic address: j.hoeks@maastrichtuniversity.nl.

Abstract

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.

KEYWORDS:

MicroRNA; Mitochondria; Oxidative capacity; Screening; Skeletal muscle metabolism; Type 2 diabetes

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