CircRNA Circ_0000118 Regulates Malignancy of Cervical Cancer Cells by Regulating miR-211-5p/miR-377-3p/AKT2 Axis

Biochem Genet. 2023 Aug;61(4):1625-1644. doi: 10.1007/s10528-023-10332-w. Epub 2023 Jan 31.

Abstract

CircRNAs are implicated in the development of several cancers. Nevertheless, the involvement of circ_0000118 in the development of cervical cancer (CC) remains unclear. Circ_0000118 levels in tumor tissues and cells were examined by qRT-PCR. The function of circ_0000118 in regulating the malignancy of CC cells was investigated using functional assays, including CCK-8, colony formation, transwell, and tube formation experiments. The functional interaction between circ_0000118 and microRNAs were validated by dual-luciferase activity assay and RNA precipitation experiments. In vivo mouse model was employed to assess the effect of circ_0000118 in the tumorigenesis of CC cells. Circ_0000118 was overexpressed in CC cells and tissues. Loss-of-function experiments demonstrated that circ_0000118 knockdown impaired the proliferation and tumor sphere formation, as well as the angiogenic potential of CC cells. RNA interaction experiments confirmed that circ_0000118 sponged miR-211-5p and miR-377-3p. AKT2 was found to be a target gene negatively modulated by miR-211-5p and miR-377-3p. AKT2 overexpression rescued the inhibition of circ_0000118 downregulation on CC cells. Our study suggested that circ_0000118 functions as an oncogenic factor in progression of CC by maintaining AKT2 level through targeting miR-211-5p and miR-377-3p as a ceRNA (competitive endogenous RNA), which provides novel therapeutic target in the management of CC.

Keywords: AKT2; Cervical cancer; Circ_0000118; miR-211-5p; miR-377-3p.

MeSH terms

  • Animals
  • Carcinogenesis
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation
  • Female
  • Humans
  • Mice
  • MicroRNAs* / genetics
  • Proto-Oncogene Proteins c-akt* / genetics
  • RNA, Circular* / genetics
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / pathology

Substances

  • AKT2 protein, human
  • MicroRNAs
  • MIRN211 microRNA, human
  • Mirn211 microRNA, mouse
  • MIRN377 microRNA, human
  • Proto-Oncogene Proteins c-akt
  • RNA, Circular
  • Mirn377 microRNA, mouse
  • Akt2 protein, mouse