Circular RNA circHECTD1 facilitates glioma progression by regulating the miR-296-3p/SLC10A7 axis

J Cell Physiol. 2021 Aug;236(8):5953-5965. doi: 10.1002/jcp.30277. Epub 2021 Feb 9.

Abstract

Glioma is the most common type of primary brain tumor. Treatment options for recurrent gliomas include surgery, chemotherapy, and radiation therapy, but the clinical outcome is usually limited. In recent years, circular RNAs have been found to play a vital role in several human cancers. Gene Expression Omnibus database was utilized to verify the differentially expressed circRNAs. Then we detected that the expression of circular RNA circHECTD1 was significantly increased. The expression and function of circHECDT1 has not yet been reported in glioma. Then we confirmed that the level of circHECTD1 was significantly increased both in glioma tissues and cell lines, which is negatively correlated with the overall survival of patients. Knockdown of circHECTD1 inhibited proliferation and invasion in vitro, and also reduced the growth of tumor and prolonged the prognosis in vivo. Knockdown of circHECTD1 significantly elevated the miR-296-3p expression in LN229 and T98G cells. Luciferase reports and RNA immunoprecipitation data indicated that miR-296-3p was a direct target of circHECTD1 and that the miR-296-3p expression negatively regulated SLC10A7. Rescue experiments showed that the overexpression of SLC10A7 could impede the effects of circHECTD1 silencing on the proliferation and invasion of glioma cells. In this study, we identified that circHECTD1 regulates SLC10A7 by interacting with miR-296-3p in glioma cells. In conclusion, this study investigated a novel biomarker panel consisting of the circHECTD1/miR-296-3p/SLC10A7 axis, which is critical for glioma tumorigenesis and invasiveness and may represent a novel therapeutic target for intervening in glioma progression.

Keywords: SLC10A7; circHECTD1; glioma; invasion; miR-296-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Neoplasms / genetics
  • Carcinogenesis / genetics
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics
  • Glioma / pathology*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics*
  • Organic Anion Transporters, Sodium-Dependent / genetics*
  • RNA, Circular / genetics
  • RNA, Circular / metabolism
  • Symporters / genetics*
  • Ubiquitin-Protein Ligases / genetics*

Substances

  • MIRN296 microRNA, human
  • MicroRNAs
  • Organic Anion Transporters, Sodium-Dependent
  • RNA, Circular
  • Slc10a7 protein, human
  • Symporters
  • HectD1 protein, human
  • Ubiquitin-Protein Ligases