PCGEM1 stimulates proliferation of osteoarthritic synoviocytes by acting as a sponge for miR-770

J Orthop Res. 2016 Mar;34(3):412-8. doi: 10.1002/jor.23046. Epub 2015 Sep 21.

Abstract

Long non-coding RNAs (lncRNAs) have been reported to play important roles in cellular metabolism and development. Various diseases have been associated with aberrant expression of lncRNAs and the related dysregulation of mRNAs. An lncRNA profiling assay was carried out to identify the key lncRNA in osteoarthritic human synoviocytes; the results revealed that prostate cancer gene expression marker 1 (PCGEM1) was significantly overexpressed in osteoarthritic synoviocytes. Exogenous overexpression of PCGEM1 inhibited apoptosis, induced autophagy, and stimulated the proliferation of human synoviocytes. The increased expression of PCGEM1 in human synoviocytes also suppressed the expression of miR-770. Transfection of the miR-770 precursor resulted in reduced proliferation, and induced apoptosis of human synoviocytes. This effect of miR-770 expression was reversed by co-introduction of PCGEM1. Target validation showed a direct binding between PCGEM1 and miR-770. We demonstrate that PCGEM1 act as sponge lncRNA for miR-770 that regulates proliferation/apoptosis and autophagy, and suggest PCGEM1 as possible target for OA therapy.

Keywords: PCGEM1; apoptosis; autophagy; miR-770; osteoarthritis; proliferation; synoviocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Proliferation
  • Male
  • Mice
  • MicroRNAs / metabolism*
  • Osteoarthritis / metabolism*
  • RNA, Long Noncoding / metabolism*
  • Synovial Membrane / metabolism*

Substances

  • MIRN-770 microRNA, human
  • MicroRNAs
  • PCGEM1 non-coding RNA, human
  • RNA, Long Noncoding