miR-194 inhibits the proliferation, invasion, migration, and enhances the chemosensitivity of non-small cell lung cancer cells by targeting forkhead box A1 protein

Oncotarget. 2016 Mar 15;7(11):13139-52. doi: 10.18632/oncotarget.7545.

Abstract

Recent studies have implied that miRNAs may play a crucial role in tumor progression and may be involved in the modulation of some drug resistance in cancer cells. Earlier studies have demonstrated that miR-194 was involved in tumor metastasis and drug resistance in non-small cell lung cancer (NSCLC), whereas their expression and roles on NSCLC still need further elucidation. In the current study, we found that miR-194 is decreased in NSCLC samples compared with adjacent non-cancerous lung samples, and low expression of miR-194 predicts poor patient survival. Both in vitro and in vivo experiments showed that ectopic stable expression miR-194 suppressed proliferation, migration, invasion and metastasis and induced apoptosis in NSCLC cells and that this suppression could be reversed by reintroducing forkhead box A1 (FOXA1), a functional target of miR-194. In addition, miR-194 was downregulated in in cisplatin-resisted human NSCLC cell line-A549/DDP and overexpression of miR-194 increases cisplatin sensitivity. These findings suggested that miR-194 inhibits proliferation and metastasis and reverses cisplatin-resistance of NSCLC cells and may be useful as a new potential therapeutic target for NSCLC.

Keywords: forkhead box A1 protein; miR-194; non-small cell lung cancer.

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • Hepatocyte Nuclear Factor 3-alpha / biosynthesis*
  • Heterografts
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics

Substances

  • FOXA1 protein, human
  • Hepatocyte Nuclear Factor 3-alpha
  • MIRN194 microRNA, human
  • MicroRNAs