CircRNA-UBE2G1 regulates LPS-induced osteoarthritis through miR-373/HIF-1a axis

Cell Cycle. 2020 Jul;19(13):1696-1705. doi: 10.1080/15384101.2020.1772545. Epub 2020 May 31.

Abstract

Osteoarthritis (OA) is a very common chronic and degenerative joint disease characterized by persistent destruction of articular cartilage. Recently, increasing evidence showed that circular RNAs (circRNAs) play critical roles in OA progression. However, the functions of circRNAs in OA and their underlying mechanisms of action remain unclear. In the present study, the expression levels of circRNA-UBE2G1 and HIF-1a were significantly increased in OA tissues, whereas miR‑373 expression was downregulated. Function assays showed that circRNA-UBE2G1 inhibition reduced the effects of LPS on C28/I2 cells viability and apoptosis. In terms of mechanism, we revealed that circRNA-UBE2G1 binds to miR‑373 as competing endogenous RNAs (ceRNAs). HIF-1a might act as a target of miR‑373. Moreover, miR‑373 suppression or HIF-1a overexpression restored the effects of circRNA-UBE2G1 downregulation on LPS-induced chondrocytes injury. Collectively, our data suggest that circRNA-UBE2G1 facilitates the progression in the LPS-induced OA cell model via regulating the miR‑373/HIF-1a axis.

Abbreviations: OA: Osteoarthritis; Circular RNAs; miRNAs: MicroRNAs; Mut: Mutant; WT: Wild type; UTR: Untranslated region.

Keywords: HIF-1a; Osteoarthritis; circRNA-UBE2G1; miR‑373.

MeSH terms

  • Cell Line
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • Chondrocytes / pathology
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Lipopolysaccharides
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Osteoarthritis / genetics*
  • Osteoarthritis / pathology
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Signal Transduction / drug effects
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Lipopolysaccharides
  • MIRN373 microRNA, human
  • MicroRNAs
  • RNA, Circular