MicroRNA-21 targets LRRFIP1 and contributes to VM-26 resistance in glioblastoma multiforme

Brain Res. 2009 Aug 25;1286:13-8. doi: 10.1016/j.brainres.2009.06.053. Epub 2009 Jun 24.

Abstract

MicroRNAs control a wide array of biological processes including cell differentiation, proliferation, and apoptosis whose dysregulation is a hallmark of cancer. MicroRNA-21 (miR-21) is overexpressed in many cancers including glioblastoma and contributes to tumor resistance to chemotherapy. We investigated whether miR-21 mediated chemoresistance to the chemotherapeutic agent VM-26 in glioblastoma cells and sought to identify the candidate target genes for miR-21 by gene expression profiling. Here we report that miR-21 was involved in mediating chemoresistance to VM-26 in glioblastoma cells. Suppression of miR-21 by specific antisense oligonucleotides in glioblastoma cell U373 MG led to enhanced cytotoxicities of VM-26 against U373 MG cells. We further identified and validated LRRFIP1, whose product is an inhibitor of NF-kappaB signaling, as a direct target gene of miR-21. Our findings suggest that miR-21 represents a promising target for therapeutic manipulation to increase the efficacy of chemotherapeutic agents in treating glioblastoma, a highly lethal type of cancer.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / drug therapy
  • Glioblastoma / genetics*
  • Humans
  • MicroRNAs / genetics*
  • RNA-Binding Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Teniposide / pharmacology*
  • Transfection

Substances

  • Antineoplastic Agents
  • LRRFIP1 protein, human
  • MIRN21 microRNA, human
  • MicroRNAs
  • RNA-Binding Proteins
  • Teniposide