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

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

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1
Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.

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.

PMID:
19559015
DOI:
10.1016/j.brainres.2009.06.053
[Indexed for MEDLINE]
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