Hsa_circ_0045714 regulates chondrocyte proliferation, apoptosis and extracellular matrix synthesis by promoting the expression of miR-193b target gene IGF1R

Hum Cell. 2017 Oct;30(4):311-318. doi: 10.1007/s13577-017-0177-7. Epub 2017 Aug 9.

Abstract

In recent years, some studies have been made on the effects of circular RNA (circRNA) in osteoarthritis (OA) and so on; however, its mechanisms remain to be further explored. Studies have shown that tumor necrosis factor-alpha can inhibit hsa_circ_0045714 expression in chondrocytes so as to upregulate miR-193b expression. Dual-luciferase reporter assay showed that insulin-like growth factor 1 receptor (IGF1R) is a key target gene of miR-193b. Hsa_circ_0045714 over-expression does not influence miR-193b expression, but can inhibit its transcriptional activity, thereby upregulating IGF1R expression. Hsa_circ_0045714 can promote the expression of type II collagen and aggrecan, and upregulate chondrocyte proliferation, while its linear sequences cannot. IGF1R has similar function, while miR-193b can inhibit the expression of type II collagen and aggrecan, and downregulate chondrocyte proliferation but enhance their apoptosis. IGF1R overexpression can reverse the effect of miR-193b, while miR-193b mimics or IGF1R siRNA can inhibit the function of hsa_circ_0045714. Therefore, hsa_circ_0045714 can regulate extracellular matrix synthesis as well as proliferation and apoptosis of chondrocytes by promoting the expression of miR-193b target gene IGF1R. The findings will provide new proofs for studies on the applications of circRNA in OA and other orthopedic diseases.

Keywords: Chondrocyte; CircRNA; IGF1R; Osteoarthritis; hsa_circ_0045714; miR-193b.

MeSH terms

  • Apoptosis / genetics*
  • Cell Proliferation / genetics*
  • Cells, Cultured
  • Chondrocytes / cytology*
  • Chondrocytes / metabolism
  • Extracellular Matrix / metabolism*
  • Gene Expression
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • RNA / physiology*
  • RNA, Circular
  • Receptor, IGF Type 1
  • Receptors, Somatomedin / genetics*
  • Receptors, Somatomedin / metabolism

Substances

  • IGF1R protein, human
  • MIRN193 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Receptors, Somatomedin
  • RNA
  • Receptor, IGF Type 1