MiR-99a-5p Constrains Epithelial-Mesenchymal Transition of Cervical Squamous Cell Carcinoma Via Targeting CDC25A/IL6

Mol Biotechnol. 2022 Nov;64(11):1234-1243. doi: 10.1007/s12033-022-00496-y. Epub 2022 May 9.

Abstract

MiR-99a-5p participates in processes and pathogenesis of varying diseases. However, the molecular mechanism of miR-99a-5p in human cervical squamous cell carcinoma (CSCC) remains unclear. Here, we found that miR-99a-5p was lowly expressed in CSCC cells and negatively associated with overall survival. In addition, cellular experiments including CCK8, wound healing, Transwell and flow cytometry assays disclosed that transfection of miR-99a-5p mimic could suppress the cell activity, cell migratory, and invasive abilities, and promote cell apoptosis, thus inhibiting the tumor progression of CSCC cells. Luciferase reporter gene assay indicated that miR-99a-5p targeted 3'-UTR of CDC25A. Also, enforced CDC25A level rescued the impact of miR-99a-5p on CSCC progression. Silencing CDC25A could restrain the mRNA and protein levels of IL-6 in CSCC. CDC25A overexpression or IL-6 treatment could attenuate inhibiting impact of miR-99a-5p overexpression on epithelial-mesenchymal transition (EMT). These findings suggested that miR-99a-5p may play an anti-tumor role in tumor metastasis by targeting CDC25A/IL6 to hamper EMT process, which revealed a novel molecular mechanism in CSCC.

Keywords: Apoptosis; IL-6; Invasion; Migration; miR-99a-5p; cervical squamous cell carcinoma (CSCC); CDC25A.

MeSH terms

  • 3' Untranslated Regions
  • Carcinoma, Squamous Cell* / genetics
  • Carcinoma, Squamous Cell* / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition* / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / metabolism
  • cdc25 Phosphatases / genetics
  • cdc25 Phosphatases / metabolism

Substances

  • 3' Untranslated Regions
  • cdc25 Phosphatases
  • CDC25A protein, human
  • Interleukin-6
  • MicroRNAs
  • MIRN99 microRNA, human