MicroRNA-21 targets LRRFIP1 and contributes to VM-26 resistance in glioblastoma multiforme.
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.
Li
Yiming
Y
Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
Li
Weiqing
W
Yang
Yongji
Y
Lu
Yicheng
Y
He
Cheng
C
Hu
Guohan
G
Liu
Huimin
H
Chen
Juxiang
J
He
Jin
J
Yu
Hongyu
H
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013713:Teniposide / Q000494:pharmacology*; D014162:Transfection
D000970:Antineoplastic Agents; C114370:LRRFIP1 protein, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D013713:Teniposide