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Updated: Jun 22, 2026

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
MicroRNA-21 targets LRRFIP1 and contributes to VM-26 resistance in glioblastoma multiforme
Yiming Li1, Weiqing Li, Yongji Yang
1Department 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.
Insights
MicroRNA-21 (miR-21) promotes glioblastoma chemoresistance. Suppressing miR-21 enhances chemotherapy effectiveness, offering a new therapeutic strategy for this lethal cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- MicroRNAs regulate crucial cellular functions; their dysregulation is linked to cancer.
- MicroRNA-21 (miR-21) is frequently overexpressed in glioblastoma, contributing to chemotherapy resistance.
Purpose of the Study:
- To investigate miR-21's role in mediating glioblastoma chemoresistance to VM-26.
- To identify miR-21 target genes using gene expression profiling.
Main Methods:
- Utilized antisense oligonucleotides to suppress miR-21 in U373 MG glioblastoma cells.
- Employed gene expression profiling to identify miR-21 target genes.
- Validated LRRFIP1 as a direct miR-21 target.
Main Results:
- miR-21 was confirmed to mediate chemoresistance to VM-26 in glioblastoma cells.
- Suppression of miR-21 significantly enhanced VM-26 cytotoxicity in U373 MG cells.
- LRRFIP1, an inhibitor of NF-kappaB signaling, was identified and validated as a direct miR-21 target.
Conclusions:
- miR-21 plays a significant role in glioblastoma chemoresistance.
- Targeting miR-21 could enhance the efficacy of chemotherapy agents like VM-26.
- miR-21 inhibition presents a promising therapeutic strategy for glioblastoma treatment.
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