CircRILPL1 promotes muscle proliferation and differentiation via binding miR-145 to activate IGF1R/PI3K/AKT pathway

Cell Death Dis. 2021 Feb 1;12(2):142. doi: 10.1038/s41419-021-03419-y.


Many novel non-coding RNAs, such as microRNAs (miRNAs) and circular RNAs (circRNAs), are involved in various physiological and pathological processes. The PI3K/AKT signaling pathway is important for its role in regulating skeletal muscle development. In this study, molecular and biochemical assays were used to confirm the role of miRNA-145 (miR-145) in myoblast proliferation and apoptosis. Based on sequencing data and bioinformatics analysis, we identified a new circRILPL1, which acts as a sponge for miR-145. The interactions between circRILPL1 and miR-145 were examined by bioinformatics, a luciferase assay, and RNA immunoprecipitation. Mechanistically, knockdown or exogenous expression of circRILPL1 in the primary myoblasts was performed to prove the functional significance of circRILPL1. We investigated the inhibitory effect of miR-145 on myoblast proliferation by targeting IGF1R to regulate the PI3K/AKT signaling pathway. A novel circRILPL1 was identified that could sponge miR-145 and is related to AKT activation. In addition, circRILPL1 was positively correlated with muscle proliferation and differentiation in vitro and could inhibit cell apoptosis. The newly identified circRILPL1 functions as a miR-145 sponge to regulate the IGF1R gene and rescue the inhibitory effect of miR-145 on the PI3K/AKT signaling pathway, thereby promoting myoblast growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cattle
  • Cell Differentiation / physiology
  • Cell Proliferation / physiology
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism*
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / growth & development
  • Muscle, Skeletal / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Receptor, IGF Type 1 / metabolism*
  • Signal Transduction
  • Transfection


  • Adaptor Proteins, Signal Transducing
  • IGF1R protein, human
  • MIRN145 microRNA, human
  • MicroRNAs
  • RILPL1 protein, human
  • Receptor, IGF Type 1
  • Proto-Oncogene Proteins c-akt