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