microRNA-141-3p fosters the growth, invasion, and tumorigenesis of cervical cancer cells by targeting FOXA2

Arch Biochem Biophys. 2018 Nov 1;657:23-30. doi: 10.1016/j.abb.2018.09.008. Epub 2018 Sep 14.

Abstract

microRNA (miR)-141-3p has context-dependent effects on tumor progression. In this study, we attempted to explore the expression and function of miR-141-3p in cervical cancer. We found that miR-141-3p expression was significantly increased in cervical cancer specimens relative to normal cervical tissues. Moreover, miR-141-3p levels were associated with tumor size and lymph node metastasis status. Ectopic expression of miR-141-3p significantly increased cervical cancer cell proliferation, colony formation, invasion, and epithelial to mesenchymal transition, whereas depletion of miR-141-3p suppressed cervical cancer cell proliferation and invasion. FOXA2 was identified to be a target of miR-141-3p. Overexpression of miR-141-3p led to a marked inhibition of endogenous FOXA2 in cervical cancer cells. FOXA2 silencing phenocopied the effects of miR-141-3p overexpression on cervical cancer cell proliferation and invasion. Enforced expression of FOXA2 blocked the effects of miR-141-3p on cervical cancer cell proliferation and invasion. miR-141-3p overexpression significantly accelerated the growth of xenograft tumors, which was accompanied by a striking reduction in FOXA2 expression. miR-141-3p acts as an oncogene in cervical cancer largely through repression of FOXA2. Targeting miR-141-3p may represent a potential therapeutic strategy for cervical cancer.

Keywords: Cervical cancer; FOXA2; Growth; Invasion; miR-141-3p.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Down-Regulation
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Hepatocyte Nuclear Factor 3-beta / genetics*
  • Humans
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Up-Regulation
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology

Substances

  • FOXA2 protein, human
  • MIRN141 microRNA, human
  • MicroRNAs
  • Hepatocyte Nuclear Factor 3-beta