Circ‑TOP2A acts as a ceRNA for miR‑346 and contributes to glioma progression via the modulation of sushi domain‑containing 2

Mol Med Rep. 2021 Apr;23(4):255. doi: 10.3892/mmr.2021.11894. Epub 2021 Feb 4.

Abstract

Dysregulated circular RNAs (circRNAs) are involved in the carcinogenesis and progression of multiple human malignancies. Knowledge of circRNAs in glioma (GM) is limited and further study to uncover new therapeutic targets for GM is urgently required. The present study demonstrated that circ‑TOP2A was elevated in GM tissue specimens and cells and that circ‑TOP2A levels indicated an unfavorable clinical prognosis in GM. Functionally, circ‑TOP2A knockdown reduced viability, migration and invasion and triggered apoptosis in LN229 cells. Ectopic expression of circ‑TOP2A aggravated these malignant behaviors in U87MG cells. In terms of mechanism, RNA‑seq was performed to discover the potential targets regulated by circ‑TOP2A. Circ‑TOP2A acted as a competing endogenous RNA to upregulate sushi domain‑containing 2 (SUSD2) expression by sponging microRNA (miR) 346. Rescue assays revealed that the oncogenic function of circ‑TOP2A was partially dependent on its regulation of the miR‑346/SUSD2 axis. In conclusion, the present study identified that circ‑TOP2A promoted GM proliferation and aggressiveness via miR‑346/SUSD2 signaling, which is a potential prognostic biomarker and therapeutic target for GM.

Keywords: glioma; circ‑TOP2A; micro RNA 346; sushi domain‑containing 2.

MeSH terms

  • Apoptosis*
  • Cell Line, Tumor
  • Cell Movement*
  • Glioma
  • Humans
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Metastasis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*

Substances

  • MIRN346 microRNA, human
  • Membrane Glycoproteins
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Circular
  • RNA, Neoplasm
  • SUSD2 protein, human