Circ_0002711 knockdown suppresses cell growth and aerobic glycolysis by modulating miR-1244/ROCK1 axis in ovarian cancer

J Biosci. 2021:46:21.

Abstract

It has been well investigated that circular RNAs (circRNAs) play important roles in various cancers. The function of circ_0002711 and its underlying mechanisms in ovarian cancer (OC) remain unknown. qRT-PCR and western blot were performed to detect the expressions of circ_0002711, microRNA-1244 (miR-1244), and Rho kinase 1 (ROCK1) in OC tissues and cells. MTT assay and colony formation assay were employed to evaluate cell proliferation. Detection of lactate production, glucose uptake, and ATP level and oxygen consumption were used to determine Warburg effect. Western blot was used to examine glycolysis or proliferationrelated genes. Dual-luciferase reporter assay and RIP pull down assay were used to address the relationship among circ_0002711, miR-1244, and ROCK1. In vivo tumor growth was evaluated in nude mice. Circ_0002711 was upregulated in OC tissues and cell lines. Circ_0002711 downregulation inhibited cell viability, colony formation ability and aerobic glycolysis. Circ_0002711 contained binding sites with miR1244. Moreover, loss of miR-1244 undermined circ_0002711 downregulation-mediated function. ROCK1 contained binding sites with miR-1244. MiR-1244 upregulation suppressed cell proliferation and aerobic glycolysis, which was rescued by enhanced expression of ROCK1. Circ_0002711 knockdown hampered ROCK1 expression by upregulating miR-1244 expression. Finally, decreased expression of circ_0002711 inhibited tumor growth in vivo. Circ_0002711/miR-1244/ROCK1 axis regulated Warburg effect and tumor growth in vivo.

MeSH terms

  • Aerobiosis
  • Animals
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Glycolysis / genetics*
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • RNA, Circular / genetics*
  • Xenograft Model Antitumor Assays
  • rho-Associated Kinases / genetics*

Substances

  • MIRN1244 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • ROCK1 protein, human
  • rho-Associated Kinases