Suppression of EIF4G2 by miR-379 potentiates the cisplatin chemosensitivity in nonsmall cell lung cancer cells

FEBS Lett. 2017 Feb;591(4):636-645. doi: 10.1002/1873-3468.12566. Epub 2017 Feb 20.

Abstract

Although microRNAs and EIF4G2 are both known to play pivotal roles in cancer progression, it remains unknown whether these pathways regulate chemosensitivity in a coordinated manner. Here, we show that miR-379 expression is significantly downregulated in chemoresistant nonsmall cell lung cancer (NSCLC) tissues and cells. Manipulation of miR-379 levels could alter the in vitro and in vivo cisplatin (CDDP) resistance in lung cancer (LCa) cells. Mechanistically, miR-379 potentiated LCa chemosensitivity via modulation of CDDP-induced apoptosis by directly targeting the EIF4G2 3'UTR. Additionally, we observed an inverse correlation between miR-379 and EIF4G2 expression in LCa tissues from patients with CDDP-based chemotherapy. Together, our findings shed new light on the potential involvement of miR-379/EIF4G2 cascade in the pathogenesis of CDDP resistance in LCa.

Keywords: EIF4F; chemoresistance; cisplatin; lung cancer; miRNAs.

MeSH terms

  • 3' Untranslated Regions / genetics
  • A549 Cells
  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Base Sequence
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Eukaryotic Initiation Factor-4G / genetics*
  • Eukaryotic Initiation Factor-4G / metabolism
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Immunoblotting
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Mice, Nude
  • MicroRNAs / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Xenograft Model Antitumor Assays

Substances

  • 3' Untranslated Regions
  • Antineoplastic Agents
  • EIF4G2 protein, human
  • Eukaryotic Initiation Factor-4G
  • MIRN379 microRNA, human
  • MicroRNAs
  • Cisplatin