ncRNA basic information
ncRNA ID:
MI0000476/MI0000455
ncRNA Database:
miRBase
ncRNA Name:
miR-138
ncRNA Type:
miRNA
ncRNA Expression:
up-regulated
ncRNA Method:
qRT-PCR
ncRNA Target Gene:
BIM
ncRNA Pathway:
NA
Evidence (ncRNA-drug):
validated
drug basic information
Drug ID:
DB00853 (APRD00557)
Drug Name:
Temozolomide
Drug Method:
In the study, we investigated the role of microRNA (miRNA) alterations as mediators of alkylator resistance in glioblastoma cells. Using microarray-based miRNA expression profiling of parental and TMZ-resistant cultures of three human glioma cell lines, we identified a set of differentially expressed miRNA candidates. From these, we selected miR-138 for further functional analyses as this miRNA was not only upregulated in TMZ-resistant versus parental cells, but also showed increased expression in vivo in recurrent glioblastoma tissue samples after TMZ/RT-TMZ treatment. Transient transfection of miR-138 mimics in glioma cells with low basal miR-138 expression increased glioma cell proliferation. Moreover, miR-138 overexpression increased TMZ resistance in long-term glioblastoma cell lines and glioma initiating cell cultures. The apoptosis regulator BIM was identified as a direct target of miR-138, and its silencing mediated the induced TMZ resistance phenotype. Altered sensitivity to apoptosis played only a minor role in this resistance mechanism. Instead, we identified the induction of autophagy to be regulated downstream of the miR-138/BIM axis and to promote cell survival following TMZ exposure.
Drug Response:
resistant
Cancer basic information
Cancer:
glioblastoma
Tissue/Cell:
cell line ( LN-18, LN-229, LN-308, LN-319, LN-428, D247MG, A172, U87MG, T98G,LN-18-R, LN-229-R and LN-308-R,ZH-161, ZH-305, T-325, T-269 and S-24 )
Other information
Title:
MicroRNA-138 promotes acquired alkylator resistance in glioblastoma by targeting the Bcl-2-interacting mediator BIM.
Journal:
Oncotarget
Published:
2016
PubMed ID:
26887050