LncRNA KCNQ1OT1 accelerates fracture healing via modulating miR-701-3p/FGFR3 axis

FASEB J. 2020 Apr;34(4):5208-5222. doi: 10.1096/fj.201901864RR. Epub 2020 Feb 14.

Abstract

Emerging evidence highlights the role of the long noncoding RNA (lncRNA) KCNQ1OT1 in fracture healing. Osteoblast proliferation, migration, and survival are pivotal during this process. In this study, we aimed to improve our understanding of the regulatory role of lncRNA KCNQ1OT1 during osteoblast proliferation, migration, and survival. We searched the gene expression omnibus databases and LncBase Experimental V.2 to identify key microRNAs (miRNAs) targets of KCNQ1OT1. MiR-701-3p was selected as a differentially expressed miRNA and RNA immunoprecipitation assays were performed to verify its interaction with KCNQ1OT1. Fibroblast growth factor receptor 3 (FGFR3) was also identified as a target of miR-701-3p. We further identified KCNQ1OT1 as a competing endogenous RNA of miR-701-3p that could influence osteoblast proliferation, migration, and apoptosis in vitro and in vivo. Taken together, our results indicate that the KCNQ1OT1/miR-701-3p/FGFR3 axis is an important regulator of osteoblast proliferation, migration, and apoptosis, and provide a new therapeutic avenue for fracture healing.

Keywords: FGFR3; apoptosis; lncRNA; miRNA; migration; osteoblast proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Proliferation
  • Disease Models, Animal*
  • Femoral Fractures / pathology
  • Femoral Fractures / therapy*
  • Fracture Healing / genetics*
  • Gene Expression Regulation, Neoplastic*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • RNA, Long Noncoding / genetics*
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics
  • Receptor, Fibroblast Growth Factor, Type 3 / metabolism*
  • Signal Transduction

Substances

  • KCNQ1OT1 RNA
  • MicroRNAs
  • RNA, Long Noncoding
  • Fgfr3 protein, mouse
  • Receptor, Fibroblast Growth Factor, Type 3