IGF2BP2, an RNA-binding protein regulates cell proliferation and osteogenic differentiation by stabilizing SRF mRNA

J Cell Physiol. 2023 Jan;238(1):195-209. doi: 10.1002/jcp.30919. Epub 2022 Nov 27.

Abstract

Osteoblast proliferation and osteogenic differentiation (OGD) are regulated by complex mechanisms. The roles in cell proliferation and OGD of RNA-binding proteins in the insulin-like growth factor 2 mRNA-binding protein (IGF2BP) family remain unclear. To elucidate this, we examined the differential expression of IGF2BP2 in OGD and osteoporosis, and the expression profile of IGF2BP2-binding RNA in vitro. We screened the GEO database for differential expression of IGF2BP in OGD and osteoporosis, and verified the RNAs interacting with IGF2BP2 via RNA immunoprecipitation sequencing assays. The proliferation and OGD of IGF2BP2- and serum response factor (SRF)-treated cells, and their regulatory mechanisms, were examined. IGF2BP2 was differentially expressed in OGD and osteoporosis. The RNA immunoprecipitation sequencing assay identified all of the RNAs that bind with IGF2BP2, and revealed SRF as a target of IGF2BP2. IGF2BP2 and SRF inhibition impaired MC3T3-E1 cell growth but promoted OGD. The mRNA stability analysis revealed that IGF2BP2 enhanced SRF mRNA stability against degradation. In summary, IGF2BP2 is a potential biomarker and therapeutic target for osteoporosis and OGD.

Keywords: IGF2BP2; RNA-binding protein; cell proliferation; osteogenic differentiation; serum response factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Humans
  • Mice
  • Osteogenesis* / genetics
  • Osteoporosis* / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism
  • Serum Response Factor* / genetics
  • Serum Response Factor* / metabolism

Substances

  • IGF2BP2 protein, human
  • RNA, Messenger
  • RNA-Binding Proteins
  • Serum Response Factor
  • SRF protein, human