CircRNA8924 Promotes Cervical Cancer Cell Proliferation, Migration and Invasion by Competitively Binding to MiR-518d-5p /519-5p Family and Modulating the Expression of CBX8

Cell Physiol Biochem. 2018;48(1):173-184. doi: 10.1159/000491716. Epub 2018 Jul 13.

Abstract

Background/aims: Circular RNAs (circRNAs) play a significant role in the development and progression of various human cancers. However, the expression and function of circRNAs in cervical cancer (CC) have rarely been explored. The aim of this study was to investigate the biological function of circRNA8924 in CC and elucidate the possible molecular mechanism involved.

Methods: Quantitative polymerase chain reaction was used to determine mRNA expression of circRNA8924, miR-518d-5p/519-5p and CBX8 in CC tissues and cells. CBX8 protein expression was measured by Western blotting. The CCK-8 assay was used to evaluate cell proliferation, and the transwell assay to determine cell migration and invasion. The luciferase reporter assay was used to determine the direct regulation of miR-518d-5p/519-5p and circRNA8924 or CBX8 Results: The study demonstrated that the expression level of circRNA8924 in CC was significantly higher than that in the adjacent normal tissues (P < 0.001), and that it was also associated with tumor size, FIGO staging and myometrial invasion. The knockdown of circRNA8924 significantly inhibited the proliferation, migration and invasion of CC cells SiHa and HeLa. The expression level of miR-518d-5p/519-5p was negatively correlated with circRNA8924, and circRNA8924 regulated CBX8 by competitively binding to miR-518d-5p/519-5p.

Conclusions: CircRNA8924 is highly expressed in CC tissue and can be considered a competitive endogenous RNA of the miR-518d-5p/519-5p family to promote the malignant biological behavior of CC cells. It is suggested that it may serve as a new biomarker for CC diagnosis and disease progression and provide potential targets for targeted therapy.

Keywords: CBX8; CeRNA; Cervical cancer; CircRNA; CircRNA8924; MiR-518d-5p/519-5p; MiRNA family.

MeSH terms

  • Antagomirs / metabolism
  • Cell Movement
  • Cell Proliferation
  • Cyclin D1 / metabolism
  • Female
  • G1 Phase Cell Cycle Checkpoints
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Humans
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Polycomb Repressive Complex 1 / genetics
  • Polycomb Repressive Complex 1 / metabolism*
  • RNA / antagonists & inhibitors
  • RNA / genetics
  • RNA / metabolism*
  • RNA Interference
  • RNA, Circular
  • RNA, Small Interfering / metabolism
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antagomirs
  • CBX8 protein, human
  • MIRN518 microRNA, human
  • MIRN519 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA, Small Interfering
  • bcl-2-Associated X Protein
  • Cyclin D1
  • RNA
  • Polycomb Repressive Complex 1