Circ-ZNF264 Promotes the Growth of Glioma Cells by Upregulating the Expression of miR-4493 Target Gene Apelin

J Mol Neurosci. 2019 Sep;69(1):75-82. doi: 10.1007/s12031-019-01334-8. Epub 2019 May 21.

Abstract

Glioma is the most common malignant tumor in the brain and nervous system, with high recurrence and high mortality rate. Recent researches have shown that circular RNAs (circRNAs) play key roles in the genesis and progress of glioma. Detection of circRNAs in glioma cells revealed that the expression of circ-ZNF264 was upregulated. At the same time, the expression of miR-4493 was downregulated in glioma cells and had multiple binding sites on the circ-ZNF264 sequence. Dual luciferase reporter gene assay confirmed that miR-4493 could bind to circ-ZNF264 and apelin specifically. MiR-4493 expression was not changed, but its target gene apelin expression could be significantly upregulated by circ-ZNF264. MiR-4493 could inhibit the expression of circ-ZNF264 and apelin. Biological behaviors of glioma cells were detected; circ-ZNF264 promoted cell proliferation and invasion and inhibited apoptosis. MiR-4493 had the opposite effects and could terminate the above effects of circ-ZNF264. When the expression of apelin was downregulated and that of circ-ZNF264 was upregulated, the changes of the above biological behaviors were not obvious. Therefore, in glioma cells, circ-ZNF264 can inhibit the function of miR-4493 and then upregulate its target gene apelin expression, thus regulating glioma cell proliferation, apoptosis, and invasion. This finding provides more evidence for the role of circRNAs in glioma.

Keywords: Apelin; Circular RNA; Glioma; miR-4493.

MeSH terms

  • Apelin / genetics*
  • Apelin / metabolism
  • Apoptosis
  • Brain Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cells, Cultured
  • Gene Expression Regulation, Neoplastic
  • Glioma / metabolism*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • RNA, Circular / genetics*
  • RNA, Circular / metabolism
  • Trans-Activators / genetics

Substances

  • APLN protein, human
  • Apelin
  • MIRN4493 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Trans-Activators