Loss of MiR-424-3p, not miR-424-5p, confers chemoresistance through targeting YAP1 in non-small cell lung cancer

Mol Carcinog. 2017 Mar;56(3):821-832. doi: 10.1002/mc.22536. Epub 2016 Aug 26.

Abstract

MiR-424 has been discovered to be involved in the chemoresistance of lung cancer. However, the underlying mechanism by which miR-424 played role in chemoresistance has been unknown. Here, in our study, to investigate the role of miR-424 in non-small cell lung cancer (NSCLC), we have detected the expression of miR-424-3p and -5p in NSCLC tissues and paired normal control. Moreover, to explore the role of miR-424-3p in NSCLC cells, miR-424-3p and -5p were both re-expressed and knocked down using transient transfection with their respective mimics and inhibitors. Cell viability, migration, and invasion were evaluated using MTT, wound-healing and Transwell assays, respectively. It was found that down-regulation of miR-424-3p was pronouncedly associated with NSCLC progression and overall prognosis; and that both miR-424-3p and -5p were markedly capable of preventing the proliferation, migration, and invasion in NSCLC cells. Additionally, it is miR-424-3p but not miR-424-5p that enhances the chemo-sensitivity of NSCLC cells through targeting YAP1. Mechanistically, YAP1 was identified as down-stream target of miR-424-3p. Together, it was for the first time in our study found that it is loss of miR-424-3p not miR-424-5p that enables chemoresistance through targeting YAP1 in NSCLC, supporting that miR-424-3p could be used as therapeutic target in the curing of NSCLC with chemoresistance. © 2016 Wiley Periodicals, Inc.

Keywords: YAP1; chemoresistance; lung cancer; miR-424-3p; miR-424-5p.

MeSH terms

  • 3' Untranslated Regions
  • A549 Cells
  • Adaptor Proteins, Signal Transducing / genetics*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Disease Progression
  • Drug Resistance, Neoplasm*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Male
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Phosphoproteins / genetics*
  • Prognosis
  • Promoter Regions, Genetic
  • Transcription Factors
  • YAP-Signaling Proteins

Substances

  • 3' Untranslated Regions
  • Adaptor Proteins, Signal Transducing
  • MIRN424 microrna, human
  • MicroRNAs
  • Phosphoproteins
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human