miR-142-5p protects against osteoarthritis through competing with lncRNA XIST

J Gene Med. 2020 Apr;22(4):e3158. doi: 10.1002/jgm.3158. Epub 2020 Feb 14.

Abstract

Background: The relevance between abnormal microRNA expression and osteoarthritis (OA) has been elaborated in recent studies. Hence, the present study aimed to assess the impact of miR-142-5p on chondrocyte growth and apoptosis.

Methods: To mimic OA-like chondrocyte damage, interleukin (IL)-1β was used for chondrocyte treatment. The expression of miR-142-5p, SGTB, long non-coding RNA (lncRNA) X inactive specific transcript (XIST) and involved molecules such as Col2A1, Bcl-2, MMP13 and Bax was determined via a quantitative reverse transcriptase-polymerase chain reaction and western blot analyses. Functional roles of miR-142-5p, SGTB and XIST were monitored in 5-ethynyl-2'-deoxyuridine, CCK-8 and TUNEL experiments. Rescue analyses were conducted to consolidate the effect of the XIST/miR-142-5p/SGTB axis on chondrocytes in OA.

Results: miR-142-5p was down-regulated in IL-1β-treated chondrocytes, whereas SGTB and XIST levels were increased. Overexpression of miR-142-5p stimulated proliferation and retarded apoptosis in IL-1β-treated chondrocytes. Meanwhile, miR-142-5p elevation was correlated with an elevation of Col2A1 and Bcl-2, as well as a decline of MMP13 and Bax. A mechanistic study showed that miR-142-5p negatively regulated SGTB expression. Moreover, we found that lncRNA XIST could relieve the inhibition of miR-142-5p on SGTB expression. Augmentation of SGTB or suppression of miR-142-5p reversed the influence of XIST depletion on chondrocyte growth and apoptosis.

Conclusions: The present study has explored the fundamental role of miR-142-5p in IL-1β-treated chondrocytes, as well as the novel molecular mechanism constituted by miR-142-5p/SGTB/XIST in OA. Potentially, the results obtained may add new insight into OA pathogenesis.

Keywords: OA; SGTB; XIST; miR-142-5p.

MeSH terms

  • Apoptosis / genetics
  • Biomarkers
  • Cell Line
  • Cell Proliferation / genetics
  • Chondrocytes / metabolism
  • Disease Susceptibility
  • Extracellular Matrix
  • Gene Expression Regulation*
  • Humans
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • MicroRNAs / genetics*
  • Osteoarthritis / genetics*
  • Osteoarthritis / pathology
  • RNA Interference*
  • RNA, Long Noncoding / genetics*

Substances

  • Biomarkers
  • IL1B protein, human
  • Interleukin-1beta
  • MIRN142 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • XIST non-coding RNA