Long non-protein coding RNA DANCR functions as a competing endogenous RNA to regulate osteoarthritis progression via miR-577/SphK2 axis

Biochem Biophys Res Commun. 2018 Jun 7;500(3):658-664. doi: 10.1016/j.bbrc.2018.04.130. Epub 2018 Apr 24.

Abstract

Long noncoding RNAs (lncRNAs) have been known to be involved in multiple diverse diseases, including osteoarthritis (OA). This study aimed to explore the role of differentiation antagonizing non-protein coding RNA (DANCR) in OA and identify the potential molecular mechanisms. The expression of DANCR in cartilage samples from patients with OA was detected using quantitative reverse transcription-polymerase chain reaction. The effects of DANCR on the viability of OA chondrocytes and apoptosis were explored using cell counting kit 8 assay and flow cytometry assay, respectively. Additionally, the interaction among DANCR, miR-577, and SphK2 was explored using dual-luciferase reporter and RIP assays. The present study found that DANCR was significantly upregulated in patients with OA. Functional assays demonstrated that DANCR inhibition suppressed the proliferation of OA chondrocytes and induced cell apoptosis. The study also showed that DANCR acted as a competitive endogenous RNA to sponge miR-577, which targeted the mRNA of SphK2 to regulate the survival of OA chondrocytes. In conclusion, the study revealed that lncRNA DANCR might promote the proliferation of OA chondrocytes and reduce apoptosis through the miR-577/SphK2 axis. Thus, lncRNA DANCR might be considered as a potential therapeutic target for OA treatment.

Keywords: Osteoarthritis; SphK2; ceRNA; lncRNA DANCR; miR-577.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Base Sequence
  • Cartilage / metabolism
  • Cartilage / pathology
  • Cell Proliferation / genetics
  • Chondrocytes / metabolism
  • Chondrocytes / pathology
  • Disease Progression*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Osteoarthritis / genetics*
  • Osteoarthritis / pathology*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction* / genetics

Substances

  • DANCR long noncoding RNA, human
  • MIRN577 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase 2, human