1. Academic Validation
  2. MiR-1290 promotes myoblast differentiation and protects against myotube atrophy via Akt/p70/FoxO3 pathway regulation

MiR-1290 promotes myoblast differentiation and protects against myotube atrophy via Akt/p70/FoxO3 pathway regulation

  • Skelet Muscle. 2021 Mar 15;11(1):6. doi: 10.1186/s13395-021-00262-9.
Ji Che  # 1 Cuidi Xu  # 2 Yuanyuan Wu 1 Peiyu Jia 1 Qi Han 1 Yantao Ma 1 Xiaolei Wang 3 Yongjun Zheng 4
Affiliations

Affiliations

  • 1 Department of Pain, Huadong Hospital, Shanghai Key Laboratory of Clinical Geriatric Medicine, Fudan University, No. 221, West YanAn Rd, Shanghai, 200040, P.R. China.
  • 2 Department of Osteoporosis and Bone Disease, Huadong Hospital, Research Section of Geriatric Metabolic Bone Disease, Shanghai Geriatric Institute, Shanghai, China.
  • 3 Department of Pain, Huadong Hospital, Shanghai Key Laboratory of Clinical Geriatric Medicine, Fudan University, No. 221, West YanAn Rd, Shanghai, 200040, P.R. China. [email protected].
  • 4 Department of Pain, Huadong Hospital, Shanghai Key Laboratory of Clinical Geriatric Medicine, Fudan University, No. 221, West YanAn Rd, Shanghai, 200040, P.R. China. [email protected].
  • # Contributed equally.
Abstract

Background: Sarcopenia is a common skeletal disease related to myogenic disorders and muscle atrophy. Current clinical management has limited effectiveness. We sought to investigate the role of miR-1290 in myoblast differentiation and muscle atrophy.

Methods: By transfecting miR-1290 into C2C12 cells, we investigated whether miR-1290 regulates myogenesis and myotube atrophy via Akt/P70 signaling pathway. MHC staining was performed to assess myoblast differentiation. Differentiation-related MHC, Myod, and Myog protein levels, and atrophy-related MuRF1 and atrogin-1 were explored by western blot. An LPS-induced muscle atrophy rat model was developed. RT-PCR was conducted to analyze miR-1290 serum levels in muscle atrophy patients and normal controls (NCs).

Results: The miR-1290 transfection increased MHC-positive cells and MHC, Myod, and Myog protein levels in the miR-1290 transfection group, demonstrating that miR-1290 promoted C2C12 myoblast differentiation. Myotube diameter in the miR-1290 transfection group was higher than in the TNF-α-induced model group. Western blot analysis showed decreased MuRF1 and atrogin-1 levels in the miR-1290 transfection group compared with the model group, demonstrating that miR-1290 protected against myoblast cellular atrophy. Luciferase assay and western blot analysis showed that miR-1290 regulation was likely caused by Akt/p70/FOXO3 phosphorylation activation. In the LPS-induced muscle atrophy rat model, miR-1290 mimics ameliorated gastrocnemius muscle loss and increased muscle fiber cross-sectional area. Clinically, miR-1290 serum level was significantly decreased in muscle atrophy patients.

Conclusions: We found that miR-1290 enhances myoblast differentiation and inhibits myotube atrophy through Akt/p70/FoxO3 signaling in vitro and in vivo. In addition, miR-1290 may be a potential therapeutic target for sarcopenia treatment.

Keywords

Akt/P70/FoxO3; Atrophy; Myoblast differentiation; miR-1290.

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