miR-25-3p reverses epithelial-mesenchymal transition via targeting Sema4C in cisplatin-resistance cervical cancer cells

Cancer Sci. 2017 Jan;108(1):23-31. doi: 10.1111/cas.13104. Epub 2016 Dec 1.

Abstract

Acquisition of epithelial-mesenchymal transition (EMT) has recently been proposed as an important contributor of drug resistance in cervical cancer cells. However, the underlying mechanisms are still unclear. MicroRNAs play a crucial role in regulating EMT. The aim of this study was to explore the potential role of miR-25-3p in regulating EMT in cisplatin-resistant (CR) cervical cancer cells. To this end, we established stable CR cervical cancer cells, HeLa-CR and CaSki-CR, and investigated the function of miR-25-3p in regulating EMT. It is found that CR cervical cancer cells possessed more EMT characteristics and demonstrated higher migratory abilities and invasiveness. miR-25-3p downregulation was also seen in HeLa-CR and CaSki-CR cells. Of note, ectopic expression of miR-25-3p reversed the EMT phenotype and sensitized CR cells to cisplatin via targeting Sema4C. Furthermore, stable overexpression of miR-25-3p in HeLa-CR cells suppressed tumor growth in mice, downregulated Sema4C and Snail, and upregulated E-cadherin compared with the control group. These results suggest that miR-25-3p is an important regulator of cervical cancer EMT and chemoresistance. Thus, upregulation of miR-25-3p could be a novel approach to treat cervical cancers that are resistant to chemotherapy.

Keywords: Cervical cancer; cisplatin; drug resistance; epithelial-mesenchymal transition; miR-25-3p.

MeSH terms

  • Animals
  • Cadherins / genetics
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm* / drug effects
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Semaphorins / genetics*
  • Snail Family Transcription Factors / genetics
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology*
  • Xenograft Model Antitumor Assays

Substances

  • Cadherins
  • MIRN25 microRNA, human
  • MicroRNAs
  • Sema4c protein, human
  • Semaphorins
  • Snail Family Transcription Factors
  • Cisplatin