ncRNA basic information
ncRNA ID:
MI0000809
ncRNA Database:
miRBase
ncRNA Name:
miR-151a
ncRNA Type:
miRNA
ncRNA Expression:
down-regulated
ncRNA Method:
qRT-PCR
ncRNA Target Gene:
XRCC4
ncRNA Pathway:
NA
Evidence (ncRNA-drug):
validated
drug basic information
Drug ID:
DB00853 (APRD00557)
Drug Name:
Temozolomide
Drug Method:
Chemoresistance blunts the effect of Temozolomide (TMZ) in the treatment of glioblastoma multiforme (GBM). Whether exosomal transfer of miRNAs derived from TMZ-resistant GBM cells could confer TMZ resistance remains to be determined. qPCR was used to determine miR-151a expression in two TMZ-resistant GBM cell lines. The direct targets of miR-151a were identified by microarray assays, bioinformatics and further RNA chromatin immunoprecipitation (RNA-ChIP) assay. We characterized exosomes from TMZ-resistant cell lines, serum and cerebrospinal fluid (CSF) and determined the effect of exosomes from TMZ-resistant cells on recipient GBM cells. miR-151a loss drove the acquisition of TMZ resistance. Restored miR-151a expression sensitized TMZ-resistant GBM cells via inhibiting XRCC4-mediated DNA repair. TMZ-resistant GBM cells conferred TMZ chemoresistance to recipient TMZ-sensitive cells in an exosomal miR-151a loss-dependent manner. Restoration of exosomal miR-151a from donor TMZ-resistant cells abolished the chemoresistance dissemination that was directed by donor TMZ-resistant cells. CSF-derived exosomes contained miRNA signatures reflective of the underlying chemoresistant status of GBMs in terms of miR-151a expression levels. Exosomal miR-151a is not only essentially a less-invasive liquid biopsy that might predict chemotherapy response, but also represents a promising therapeutic target for therapy-refractory GBMs.
Drug Response:
resistant
Cancer basic information
Cancer:
glioblastoma
Tissue/Cell:
cell line (U87, U251, T98G, LN229 and A172 )
Other information
Title:
Exosomal transfer of miR-151a enhances chemosensitivity to temozolomide in drug-resistant glioblastoma.
Journal:
Cancer Lett
Published:
2018
PubMed ID:
30102952