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Research Paper|Volume 12, Issue 23|pp 24033—24056

lncRNA DLEU2 acts as a miR-181a sponge to regulate SEPP1 and inhibit skeletal muscle differentiation and regeneration

Yao Wang1, Zhi-Jie Zhao3, Xue-Ran Kang4, Tao Bian5, Zhe-Min Shen6, Yang Jiang7, Bao Sun5, Han-Bing Hu8, Yi-Sheng Chen2
  • 1Department of Orthopedics, Jinshan Hospital of Fundan University, Shanghai Medical College of Fudan University, Shanghai, China
  • 2Department of Surgery, Jinshan Hospital of Fundan University, Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 3Department of Neurosurgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
  • 4Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Ear Institute, Shanghai JiaoTong University School of Medicine, Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases, Shanghai, China
  • 5Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 6Department of General Surgery, Jinshan Hospital of Fundan University, Shanghai Medical College of Fudan University, Shanghai, China
  • 7Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 8Center of Emergency and Intensive Care Unit, Jinshan Hospital of Fudan University, Shanghai, China
* Equal contribution
Received: May 1, 2020Accepted: August 19, 2020Published: November 18, 2020
https://doi.org/10.18632/aging.104095

Copyright: © 2020 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Sarcopenia is a serious public health problem associated with the loss of muscle mass and function. The purpose of this study was to identify molecular markers and construct a ceRNA pathway as a significant predictor of sarcopenia. We designed a prediction model to select important differentially expressed mRNAs (DEMs), and constructed a sarcopenia associated ceRNA network. After correlation analysis of each element in the ceRNA network based on clinical samples and GTEX database, C2C12 mouse myoblasts were used as a model to verify the identified ceRNA pathways. A new model for predicting sarcopenia based on four molecular markers SEPP1, SV2A, GOT1, and GFOD1 was developed. The model was used to construct a ceRNA network and showed high accuracy. Correlation analysis showed that the expression levels of lncDLEU2, SEPP1, and miR-181a were closely associated with a high risk of sarcopenia. lncDLEU2 inhibits muscle differentiation and regeneration by acting as a miR-181a sponge regulating SEPP1 expression. In this study, a highly accurate prediction tool was developed to improve the prediction outcomes of sarcopenia. These findings suggest that the lncDLEU2-miR-181a-SEPP1 pathway inhibits muscle differentiation and regeneration. This pathway may be a new therapeutic target for the treatment of sarcopenia.