Downregulation of hsa_circ_0007534 restricts the proliferation and invasion of cervical cancer through regulating miR-498/BMI-1 signaling

Life Sci. 2019 Oct 15;235:116785. doi: 10.1016/j.lfs.2019.116785. Epub 2019 Aug 21.

Abstract

Aims: Hsa_circ_0007534 has been reported to be a novel cancer-related circRNA affecting multiple cancers. However, little is known about the role of hsa_circ_0007534 in cervical cancer specifically. In the current study, we aimed to explore the expression and function of hsa_circ_0007534 in cervical cancer.

Main methods: The expression of circRNA, miRNA and mRNA was measured using real-time quantitative polymerase chain reactions. Protein expression was assessed by Western blot. Knockdown of has_circ_0007534 was achieved by siRNA-mediated gene silencing. Cell proliferation was determined using a cell counting kit-8 and colony formation assays. Cell invasion was assessed using a Transwell invasion assay. RNA interactions were measured using an RNA pull-down and dual-luciferase reporter assays.

Key findings: The expression of hsa_circ_0007534 was upregulated in cervical cancer tissues and cell lines. Depletion of hsa_circ_0007534 decreased both the proliferation and invasion of cervical cancer cells. MicroRNA-498 (miR-498) was identified as a target of the miRNA encoded by hsa_circ_0007534. Levels of miR-498 were decreased in cervical cancer tissues, a finding that was inversely correlated with hsa_circ_0007534 expression. miR-498 overexpression repressed the proliferation and invasion of cervical cancer cells. B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) was verified as a target gene of miR-498. BMI-1 overexpression reversed the effects of hsa_circ_0007534 depletion or miR-498 overexpression on cervical cancer cell proliferation and invasion.

Significance: Our study demonstrates that downregulation of hsa_circ_0007534 represses the proliferation and invasion of cervical cancer through regulating the miR-498/BMI-1 axis, suggesting the hsa_circ_0007534/miR-498/BMI-1 axis as a potential therapeutic target to treat cervical cancer.

Keywords: BMI-1; Cervical cancer; hsa_circ_0007534; miR-498.

MeSH terms

  • Cell Movement*
  • Cell Proliferation*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Polycomb Repressive Complex 1 / genetics
  • Polycomb Repressive Complex 1 / metabolism*
  • RNA / genetics*
  • RNA, Circular
  • Signal Transduction
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology*

Substances

  • BMI1 protein, human
  • MIRN498 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA
  • Polycomb Repressive Complex 1