MicroRNA-154-5p suppresses cervical carcinoma growth and metastasis by silencing Cullin2 in vitro and in vivo

PeerJ. 2023 Jun 27:11:e15641. doi: 10.7717/peerj.15641. eCollection 2023.

Abstract

Background: MicroRNA-154-5p (miR-154-5p) plays a role in tumorigenesis in diverse human malignancies. Nevertheless, little is known about the mechanism by which miR-154-5p alters the growth and metastasis of cervical cancer. This research aimed to analyze the role of miR-154-5p in the pathology of cervical cancer in vitro and in vivo.

Methods: The level of miR-154-5p in human papillomavirus 16 positive cervical cancer cells was examined by real-time quantitative polymerase chain reaction. Bioinformatics predicted the downstream targets and potential functions of miR-154-5p. Furthermore, lentiviral technology was used to construct SiHa cell lines with stable up- and down-expression levels of miR-154-5p. Its differential expression effects on the progress and metastasis of cervical cancer were analyzed using cell culture and animal models.

Results: MiR-154-5p showed low expression in cervical cancer cells. Overexpression of miR-154-5p could markedly inhibit the proliferation, migration, and colony formation ability of SiHa cells, concomitantly leading to G1 arrest of the cell cycle, while silencing miR-154-5p triggered the opposite results. Meanwhile, overexpression of miR-154-5p restrained the growth and metastasis of cervical cancer by silencing CUL2 in vivo. Additionally, miR-154-5p reduced CUL2 level, and overexpression of CUL2 influenced the effect of miR-154-5p in cervical cancer. In conclusion, miR-154-5p restrained the growth and metastasis of cervical cancer by directly silencing CUL2.

Keywords: Cervical cancer; Cullin2; Growth; Metastasis; MicroRNA-154-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cullin Proteins* / genetics
  • Female
  • Gene Silencing
  • Humans
  • MicroRNAs* / genetics
  • Neoplasm Metastasis
  • Uterine Cervical Neoplasms* / genetics

Substances

  • MicroRNAs
  • MIRN154 microRNA, human
  • CUL2 protein, human
  • Cullin Proteins

Grants and funding

This research was funded by the National Natural Science Foundation of China (Grant no. 81702583), the Outstanding Youth Fund Project of Shanxi Province (Grant no. 201901D211506), the China Postdoctoral Science Foundation (Grant no. 2019M651072) and the Research Project Supported by Shanxi Scholarship Council of China (Grant no. 2022-195). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.