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

Aging (Albany NY). 2020 Nov 18;12(23):24033-24056. doi: 10.18632/aging.104095. Epub 2020 Nov 18.

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.

Keywords: DLEU2; SELENOP protein (SEPP1); competing endogenous RNA (ceRNA); miR-181a; sarcopenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Cell Differentiation*
  • Cell Line
  • Databases, Genetic
  • Female
  • Gene Regulatory Networks
  • Humans
  • Male
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Muscle Development*
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Regeneration*
  • Sarcopenia / genetics
  • Sarcopenia / metabolism*
  • Sarcopenia / pathology
  • Sarcopenia / physiopathology
  • Selenoprotein P / genetics
  • Selenoprotein P / metabolism*
  • Signal Transduction
  • Transcriptome

Substances

  • DLEU2 lncRNA, human
  • MIRN-181 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SELENOP protein, human
  • Selenop protein, mouse
  • Selenoprotein P
  • mirn181 microRNA, mouse