Circular RNA circ0001955 promotes cervical cancer tumorigenesis and metastasis via the miR-188-3p/NCAPG2 axis

J Transl Med. 2023 May 29;21(1):356. doi: 10.1186/s12967-023-04194-4.

Abstract

Background: Circular RNAs (circRNAs) are known to play a crucial role in a variety of malignancies. However, the precise role of circRNAs in cervical squamous cell carcinoma (CSCC) remains largely unknown.

Methods: The expression of circ0001955 was determined by real-time quantitative PCR and fluorescence in situ hybridization. To examine the effects of circ0001955 on CSCC metastasis and growth, functional experiments were conducted in vitro and in vivo. Mechanistically, nucleocytoplasmic separation, dual luciferase reporter assay, RNA antisense purification experiments, and rescue experiments were performed to confirm the interaction between circ0001955, miR-188-3p, and NCAPG2 in CSCC.

Results: Here, we demonstrated that a circRNA derived from the CSNK1G1 gene (circ0001955) is significantly upregulated in CSCC. The overexpression of circ0001955 promotes tumor proliferation and metastasis, whereas the knockdown of circ0001955 exerts the opposite effects. Mechanistically, circ0001955 competitively binds miR-188-3p and prevents miR-188-3p from reducing the levels of NCAPG2, activating the AKT/mTOR signaling pathway to induce epithelial mesenchymal transformation. Notably, the application of an inhibitor of mTOR significantly antagonized circ0001955-mediated CSCC tumorigenesis.

Conclusion: circ0001955 promotes CSCC tumorigenesis and metastasis via the miR-188-3p/NCAPG2 axis which would provide an opportunity to search new therapeutic targets for CSCC.

Keywords: AKT-mTOR pathway; NCAPG2; cervical squamous cell carcinoma; circ0001955; miR-188-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • In Situ Hybridization, Fluorescence
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Circular / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Uterine Cervical Neoplasms* / genetics

Substances

  • RNA, Circular
  • MicroRNAs
  • TOR Serine-Threonine Kinases
  • NCAPG2 protein, human
  • Chromosomal Proteins, Non-Histone
  • MIRN188 microRNA, human