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
- 1 Department of Orthopedics, Jinshan Hospital of Fundan University, Shanghai Medical College of Fudan University, Shanghai, China
- 2 Department of Surgery, Jinshan Hospital of Fundan University, Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- 3 Department of Neurosurgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
- 4 Department 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
- 5 Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- 6 Department of General Surgery, Jinshan Hospital of Fundan University, Shanghai Medical College of Fudan University, Shanghai, China
- 7 Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- 8 Center of Emergency and Intensive Care Unit, Jinshan Hospital of Fudan University, Shanghai, China
Received: May 1, 2020 Accepted: August 19, 2020 Published: November 18, 2020
https://doi.org/10.18632/aging.104095How to Cite
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.
Abbreviations
BMD: Bone mineral density; BPs: biological processes; CCs: cellular components; ceRNA: competing endogenous RNA; CIs: confidence intervals; DE-miRNAs: differentially expressed micro-RNAs; DEMs: differentially expressed mRNAs; EDU assays: 5-ethynyl-2’-deoxyuridine assays; EV: empty vector; GEO: Gene Expression Omnibus; GFOD1: glucose-fructose oxidoreductase domain containing 1 protein; GTEX: Genotype-Tissue Expression; GO: gene ontology; GSEA: Gene Set Enrichment Analysis; LASSO: the least absolute shrinkage and selection operator; lncRNAs: long noncoding RNAs; NC: normal control; KEGG: Kyoto Encyclopedia of Genes and Genomes; mRNAs: expressed messenger RNAs; PPI: protein-protein interaction; SEPP1: SELENOP protein; SV2A: synaptic vesicle membrane protein 2A.