miR-18a induces myotubes atrophy by down-regulating IgfI

• Published in: The international journal of biochemistry & cell biology Vol. 90; pp. 145 - 154
• Main Authors: Liu, Chuncheng, Wang, Meng, Chen, Min, Zhang, Kuo, Gu, Lijie, Li, Qiuyan, Yu, Zhengquan, Li, Ning, Meng, Qingyong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.09.2017
• Subjects: Animals; Atrophy; Base Sequence; Cell Line; Down-Regulation - genetics; hypertrophy; Igf1; Insulin-Like Growth Factor I - genetics; Mice; MicroRNAs - genetics; miR-18a; Muscle Fibers, Skeletal - metabolism; muscle physiology; muscles; muscular atrophy; Muscular Atrophy - genetics; myoblasts; Myotubes; phosphorylation; postnatal development; protein degradation; protein synthesis; skeletal muscle; Atrophy; MYHC; Myotubes; CTSL; MuRF1; Igf1; miR-18a
• ISSN: 1357-2725; 1878-5875; 1878-5875
• DOI: 10.1016/j.biocel.2017.07.020

•Overexpression of miR-18a induces myotubes atrophy and increases the expression of MuRF1, Atrogin-1 and CTSL.•And the phosphorylation of both Akt and FoxO3 are both inhibited by miR-18a, well an inhibitor of the PI3K/Akt pathway blocks the function of miR-18a.•An analysis of miR-18a targets reveals that Igf1 is regulated by miR-18a. miR-18a suppresses the expression of Igf1 in a 3′UTR-dependent manner. Muscle atrophy occurs when there is a net loss of muscle mass, leading to a change in the balance between protein synthesis and protein degradation. Igf1 is important for protein synthesis in muscle cells and can induce local skeletal muscle hypertrophy and attenuate age-related skeletal muscle atrophy via the PI3K/Akt pathway in mice, consequently restoring and improving muscle mass and strength. In this study, we show that miR-18a expression is down-regulated during C2C12 myoblast differentiation and mouse tibialis anterior muscle postnatal development. Functional studies show that forced expression of miR-18a induces myotubes atrophy and increases the expression of MuRF1, Atrogin-1 and CTSL. miR-18a also decreases the phosphorylation of both Akt and FoxO3, and an inhibitor of the PI3K/Akt pathway blocks the function of miR-18a. An analysis of miR-18a targets reveals that Igf1 is regulated by miR-18a. miR-18a suppresses the expression of Igf1 in a 3′UTR-dependent manner. These findings strongly support the idea that miR-18a has a functional role in muscle physiology and suggest that miR-18a is a potential novel therapeutic target for skeletal muscle atrophy.