MicroRNA-19a/b regulates multidrug resistance in human gastric cancer cells by targeting PTEN

Biochem Biophys Res Commun. 2013 May 10;434(3):688-94. doi: 10.1016/j.bbrc.2013.04.010. Epub 2013 Apr 16.

Abstract

Multidrug resistance (MDR) is the major cause of failure of gastric cancer chemotherapy. Members of the miR-17-92 cluster, including miR-19a/b, are considered oncomiRs and influence multiple aspects of the malignant phenotype of gastric cancer. However, the role of miR-19a/b in MDR in gastric cancer and its underlying mechanism remain unclear. In this study, we found that miR-19a/b were upregulated in MDR cell lines. Our results also showed that miR-19a/b upregulation decreased the sensitivity of gastric cancer cells to anticancer drugs. We further confirmed that miR-19a/b accelerated the ADR efflux of gastric cancer cells by increasing the levels of mdr1 and P-gp and that miR-19a/b suppressed drug-induced apoptosis by regulating Bcl-2 and Bax. Finally, we verified that PTEN, an inhibitor of AKT phosphorylation, is the functional target of miR-19a/b. Overall, these findings demonstrated that miR-19a/b promote MDR in gastric cancer cells by targeting PTEN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Adenocarcinoma / pathology*
  • Base Sequence
  • Blotting, Western
  • Cell Line, Tumor
  • DNA Primers
  • Drug Resistance, Multiple / genetics*
  • Humans
  • MicroRNAs / physiology*
  • Real-Time Polymerase Chain Reaction
  • Stomach Neoplasms / pathology*
  • Up-Regulation

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • DNA Primers
  • MIRN19 microRNA, human
  • MicroRNAs