miR-513a-3p sensitizes human lung adenocarcinoma cells to chemotherapy by targeting GSTP1

Lung Cancer. 2012 Sep;77(3):488-94. doi: 10.1016/j.lungcan.2012.05.107. Epub 2012 Jun 30.

Abstract

Cisplatin is a classic chemotherapy agent used for treating human non-small cell lung cancer (NSCLC). However, cisplatin resistance is a challenge against successful clinical use. Glutathione S-transferase P1 (GSTP1) has been reported to contribute to cisplatin resistance in many studies. MicroRNAs (miRNAs) are short non-coding RNAs that are 21-25 nucleotides in length. They play a role in post-transcriptional gene regulation by inducing repression and/or mRNA degradation. Recent studies have shown that miRNAs are responsible for cisplatin resistance. This study aims to determine whether deregulated miRNAs can sensitize human lung adenocarcinoma cells to cisplatin by targeting GSTP1. Real-time RT-PCR revealed that GSTP1 mRNA expression was 2.7 ± 0.38 folds (p=0.039) upregulated in A549/CDDP cells, compared with the parental A549 cells, while miR-513a-3p expression was 0.34 ± 0.03 folds (p=0.023) downregulated. Luciferase activity assay proved that GSTP1 was a target gene of miR-513a-3p, which was confirmed by Western blot analysis. Furthermore, CCK-8 assay showed that overexpression of miR-513a-3p could enhance cisplatin-induced apoptosis in human lung adenocarcinoma cell lines, A549/CDDP and SPC-A-1. In conclusion, our data demonstrated that miR-513a-3p can sensitize human lung adenocarcinoma cells to cisplatin by targeting GSTP1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma of Lung
  • Antineoplastic Agents / pharmacology*
  • Binding Sites
  • Cell Line, Tumor / drug effects
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm
  • Genes, Reporter
  • Glutathione S-Transferase pi / genetics*
  • Glutathione S-Transferase pi / metabolism
  • HEK293 Cells
  • Humans
  • Inhibitory Concentration 50
  • Luciferases / biosynthesis
  • Luciferases / genetics
  • Lung Neoplasms / drug therapy*
  • MicroRNAs / physiology*
  • RNA Interference
  • Transcription, Genetic

Substances

  • 3' Untranslated Regions
  • Antineoplastic Agents
  • MIRN513 microRNA, human
  • MicroRNAs
  • Luciferases
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Cisplatin