microRNA-378 promotes autophagy and inhibits apoptosis in skeletal muscle

• DOI: 10.1073/pnas.1803377115
• Publication Date: 2018-10-29T19:09:08Z
• Authors: Yan Li; Jingjing Jiang; Wei Liu; Hui Wang; Lei Zhao; Shengnan Liu; Peng Li; Shengjie Zhang; Chao Sun; Yuting Wu; Shuxian Yu; Xihua Li; Hui Zhang; Haifeng Qian; Duo Zhang; Feifan Guo; Qiwei Zhai; Qiurong Ding; Li Wang; Hao Ying
• Keywords: Male; Mice, Knockout; 0301 basic medicine; Muscle Cells; Forkhead Box Protein O1; TOR Serine-Threonine Kinases; Apoptosis; Caspase 9; Running; 3-Phosphoinositide-Dependent Protein Kinases; Mice; MicroRNAs; 03 medical and health sciences; Stress, Physiological; Autophagy; Animals; Autophagy-Related Protein-1 Homolog; 14. Life underwater; Muscle, Skeletal; Signal Transduction

The metabolic regulation of cell death is sophisticated. A growing body evidence suggests the existence multiple checkpoints that dictate fate in response to fluctuations. However, whether microRNAs (miRNAs) are able respond stress, reset threshold death, and attempt reestablish homeostasis largely unknown. Here, we show miR-378/378* KO mice cannot maintain normal muscle weight have poor running performance, which accompanied by impaired autophagy, accumulation abnormal mitochondria, excessive apoptosis skeletal muscle, whereas miR-378 overexpression enhance autophagy repress mice. Our vitro data stress-responsive promotes inhibits a cell-autonomous manner. Mechanistically, initiation through mammalian target rapamycin (mTOR)/unc-51-like activating kinase 1 (ULK1) pathway sustains via Forkhead box class O (FoxO)-mediated transcriptional reinforcement targeting phosphoinositide-dependent protein (PDK1). Meanwhile, suppresses intrinsic directly an initiator caspase-Caspase 9. Thus, propose critical component checkpoints, integrates information into adaptive reduce propensity myocytes undergo enhancing autophagic process blocking apoptotic initiation. Lastly, our suggest inflammation-induced down-regulation might contribute pathogenesis dystrophy.