MicroRNA-374c-5p regulates the invasion and migration of cervical cancer by acting on the Foxc1/snail pathway

Biomed Pharmacother. 2017 Oct;94:1038-1047. doi: 10.1016/j.biopha.2017.07.150. Epub 2017 Aug 12.

Abstract

Some microRNAs (miRNAs) have been implicated in cervical cancer development and progression. However, the roles and mechanisms of several miRNAs in epithelial-mesenchymal transition (EMT) in cervical cancer remain poorly understood. Here, we conducted a microarray analysis and found that miR-374c-5p was most down-regulated miRNA in TGFβ1-treated cervical cancer cells compared to the expression in parental cell lines. Ectopic overexpression of miR-374c-5p inhibited cervical cancerl invasion and migration in TGFβ1- treated cervical cancer cells. Conversely, miR-374c-5p knockdown increased the migration and invasion abilities of parental cell lines. Moreover, miR-374c-5p exerted its function by directly targeting the FOXC1 3/-UTR and repressing FOXC1 expression, thus leading to suppression of snail. In clinical cervical cancer samples, lower miR-374c-5p expression predicted poor patient survival and highe lymph node metastasis in cervical cancers. miR-374c-5p was negatively correlated with FOXC1, which was upregulated in cervical cancers with lymph node metastasis. Taken together, our findings highlight the important role of miR-374c-5p in regulating cervical cancers metastasis by targeting FOXC1, suggesting that miR-374c-5p may represent a novel potential therapeutic target and prognostic marker in cervical cancers.

Keywords: Cervical cancers; FOXC1; Metastasis; Prognosis; miR-374c-5p.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Epithelial-Mesenchymal Transition / physiology
  • Female
  • Forkhead Transcription Factors / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • HeLa Cells
  • Humans
  • Lymphatic Metastasis / genetics*
  • MicroRNAs / genetics*
  • Middle Aged
  • Snail Family Transcription Factors / genetics*
  • Up-Regulation / genetics
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology

Substances

  • 3' Untranslated Regions
  • FOXC1 protein, human
  • Forkhead Transcription Factors
  • MicroRNAs
  • Snail Family Transcription Factors