The Effects and Molecular Mechanisms of MiR-106a in Multidrug Resistance Reversal in Human Glioma U87/DDP and U251/G Cell Lines

PLoS One. 2015 May 7;10(5):e0125473. doi: 10.1371/journal.pone.0125473. eCollection 2015.

Abstract

Chemotherapy resistance is one of the major obstacles to effective glioma therapy. Currently, the mechanism underlying chemotherapy resistance is unclear. A recent study showed that miR-106a is an important molecule involved in chemotherapy resistance. To explore the effects and mechanisms of miR-106a on multidrug resistance reversal in human glioma cells, we silenced miR-106a expression in the cisplatin-resistant U87 (U87/DDP) and the gefitinib-resistant U251 (U251/G) glioma cell lines and measured the resulting drug sensitivity, cell apoptosis rate and rhodamine 123 content. In addition, we detected decreased expression of P-glycoprotein, MDR1, MRP1, GST-π, CDX2, ERCC1, RhoE, Bcl-2, Survivin and Topo-II, as well as reduced production of IL-6, IL-8 and TGF-β in these cell lines. Furthermore, we found decreased expression of p-AKT and transcriptional activation of NF-κB, Twist, AP-1 and Snail in these cell lines. These results suggest that miR-106a is a promising therapeutic target for the treatment of human multidrug resistant glioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Gefitinib
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioma / drug therapy
  • Glioma / genetics*
  • Humans
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / genetics
  • Quinazolines / pharmacology

Substances

  • Antineoplastic Agents
  • MIRN106 microRNA, human
  • MicroRNAs
  • Quinazolines
  • Cisplatin
  • Gefitinib

Grants and funding

This study was supported by National Natural Science Foundation of China (Grant No. 81201657). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.