Regulation of IRS1/Akt insulin signaling by microRNA-128a during myogenesis
- 1 January 2013
- journal article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 126 (12), 2678-2691
- https://doi.org/10.1242/jcs.119966
Abstract
Skeletal muscle possesses a strong ability to regenerate following injury, a fact that has been largely attributed to satellite cells. Satellite cells are skeletal muscle stem cells located beneath the basal lamina of the myofiber and are the principal cellular source of growth and regeneration in skeletal muscle. MicroRNAs (miRNAs) play key roles in modulating several cellular processes by targeting multiple mRNAs that comprise of a single or multiple signaling pathway. Several miRNAs have been shown to regulate satellite cell activity, such as miRNA-489 which functions to maintain satellite cells in a quiescent state. While muscle-specific miRNAs have been identified, many of the molecular mechanisms that regulate myogenesis that are regulated by miRNAs still remain unknown. In this study, we have shown that miR-128a is highly expressed in brain and skeletal muscle, and increases during myoblast differentiation. MiR-128a was found to regulate the target genes involved in insulin signaling, which include: Insr, Irs1, and Pik3r1 at both the mRNA and protein level. Overexpression of miR-128a in myoblasts inhibited cell proliferation by targeting IRS1. Conversely, inhibition of miR-128a induced myotube maturation and myofiber hypertrophy in vitro and in vivo. Moreover, our results demonstrate that miR-128a expression levels are negatively controlled by tumor necrosis factor-alpha (TNF-α). TNF-α promoted myoblast proliferation and myotube hypertrophy by facilitating IRS1/Akt signaling via a direct decrease of miR-128a expression in both myoblasts and myotubes. In summary, we demonstrate that miR-128a regulates myoblast proliferation and myotube hypertrophy, and provides a novel mechanism through which IRS1-dependent insulin signaling is regulated in skeletal muscle.Keywords
This publication has 67 references indexed in Scilit:
- Identification of a Novel microRNA That Regulates the Proliferation and Differentiation in Muscle Side Population CellsStem Cells and Development, 2012
- An IGF1/insulin receptor substrate-1 pathway stimulates a mitotic kinase (cdk1) in the uterine epithelium during the proliferative response to estradiolJournal of Endocrinology, 2010
- MicroRNA-214 Promotes Myogenic Differentiation by Facilitating Exit from Mitosis via Down-regulation of Proto-oncogene N-rasOnline Journal of Public Health Informatics, 2010
- The widespread regulation of microRNA biogenesis, function and decayNature Reviews Genetics, 2010
- MicroRNA 128a Increases Intracellular ROS Level by Targeting Bmi-1 and Inhibits Medulloblastoma Cancer Cell Growth by Promoting SenescencePLOS ONE, 2010
- TNF-α increases protein content in C2C12and primary myotubes by enhancing protein translation via the TNF-R1, PI3K, and MEKAmerican Journal of Physiology-Endocrinology and Metabolism, 2008
- Myoblast transfer therapy: is there any light at the end of the tunnel?2005
- NF-κB mediates the protein loss induced by TNF-α in differentiated skeletal muscle myotubesAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2000
- Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy geneNature, 1986
- Myoblast senescence in muscular dystrophyExperimental Cell Research, 1985