LncRNA PVT1 Regulates Chondrocyte Apoptosis in Osteoarthritis by Acting as a Sponge for miR-488-3p

DNA Cell Biol. 2017 Jul;36(7):571-580. doi: 10.1089/dna.2017.3678. Epub 2017 May 18.

Abstract

Long noncoding RNAs (lncRNAs) have been known to be involved in multiple diverse diseases, including osteoarthritis (OA). The present study aims at exploring the biological role of lncRNA plasmacytoma variant translocation 1 (PVT1) in OA and the underlying mechanism. Results showed that the expression of PVT1 was upregulated in OA chondrocytes compared with normal chondrocytes, silencing PVT1 inhibited the apoptosis of OA chondrocytes, and overexpression of PVT1 promoted the apoptosis of normal chondrocytes. To further investigate the underlying mechanism, miR-488-3p was predicted to be a targeted microRNA of PVT1. Different methods, including MS2 RNA immunoprecipitation (RIP), luciferase activity, and anti-AGO2 RIP, were performed to detect the interaction between PVT1 and miR-488-3p, which suggested that PVT1 negatively regulated miR-488-3p in OA chondrocytes. Moreover, PVT1 promoted the apoptosis of OA and normal chondrocytes through miR-488-3p. Collectively, this study revealed that lncRNA PVT1 regulated the apoptosis of chondrocytes by acting as a sponge for miR-488-3p in OA. PVT1 may be considered a new therapeutic target for the treatment of OA.

Keywords: PVT1; chondrocytes; long noncoding RNAs; miRNA-488-3p; osteoarthritis.

MeSH terms

  • Apoptosis
  • Argonaute Proteins / genetics*
  • Argonaute Proteins / metabolism
  • Binding Sites
  • Cartilage, Articular / metabolism*
  • Cartilage, Articular / pathology
  • Chondrocytes / metabolism*
  • Chondrocytes / pathology
  • Gene Expression Regulation
  • Genes, Reporter
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Oligoribonucleotides / genetics
  • Oligoribonucleotides / metabolism
  • Osteoarthritis / genetics*
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology
  • Primary Cell Culture
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Signal Transduction

Substances

  • AGO2 protein, human
  • Argonaute Proteins
  • MIRN488 microRNA, human
  • MicroRNAs
  • Oligoribonucleotides
  • PVT1 long-non-coding RNA, human
  • RNA, Long Noncoding
  • Luciferases