CircRNA AFF4 promotes osteoblast cells proliferation and inhibits apoptosis via the Mir-7223-5p/PIK3R1 axis

Aging (Albany NY). 2019 Dec 17;11(24):11988-12001. doi: 10.18632/aging.102524. Epub 2019 Dec 17.

Abstract

Fracture healing is a complex process involving various cell types, cytokines, and mRNAs. Here, we report the roles of the circRNA AFF4/miR-7223-5p/PIK3R1 axis during fracture healing. We found that increased expression of PIK3R1 during fracture healing is directly associated with augmented proliferation and decreased apoptosis of MC3T3-E1 cells. Furthermore, miR-7223-5p targeted PI3KR1 and inhibited MC3T3-E1 proliferation while promoting apoptosis. CircRNA AFF4 acted as a sponge of miR-7223-5p, thereby promoting MC3T3-E1 cell proliferation and inhibiting apoptosis. Local injection of circRNA AFF4 into femoral fracture sites promoted fracture healing in vivo while the injection of miR-7223-5p delayed healing. These findings suggest that CircRNA AFF4 promotes fracture healing by targeting the miR-7223-5p/PIK3R1 axis, and suggests miR-7223-5p, CircRNA AFF4, and the miR-7223-5p/PIK3R1 axis are potential therapeutic targets for improving fracture healing.

Keywords: circRNA; fracture healing; miRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Apoptosis / genetics
  • Cell Proliferation / genetics
  • Class Ia Phosphatidylinositol 3-Kinase / metabolism*
  • Fracture Healing / genetics*
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • Osteoblasts / physiology*
  • RNA, Circular / genetics*
  • Transcriptional Elongation Factors / genetics*

Substances

  • Aff4 protein, mouse
  • MicroRNAs
  • RNA, Circular
  • Transcriptional Elongation Factors
  • Class Ia Phosphatidylinositol 3-Kinase
  • Pik3r1 protein, mouse