Experiment Detail



Experiment IDEXP00174
ReferenceTitle: miR-181d: a predictive glioblastoma biomarker that downregulates MGMT expression.
Author: Zhang W, Zhang J, Hoadley K, Kushwaha D, Ramakrishnan V, Li S, Kang C, You Y, Jiang C, Song SW, Jiang T, Chen CC.
Journal: Neuro Oncol. 2012 Jun;14(6):712-9. doi: 10.1093/neuonc/nos089. Epub 2012 May 8.
Abstract: Genome-wide microRNA (miRNA) profiling of 82 glioblastomas demonstrated thatmiR-181d was inversely associated with patient overall survival after correcting for age, Karnofsky performance status, extent of resection, and temozolomide(TMZ) treatment. This association was validated using the Cancer Genome Atlas(TCGA) dataset (n= 424) and an independent cohort (n= 35). In these independentcohorts, an association of miR-181d with survival was evident in patients whounderwent TMZ treatment but was not observed in patients without TMZ therapy.Bioinformatic analysis of potential genes regulated by miR-181d revealedmethyl-guanine-methyl-transferase (MGMT) as a downstream target. Indeed,transfection of miR-181d downregulated MGMT mRNA and protein expression.Furthermore, luciferase reporter assays and coprecipitation studies showed adirect interaction between miR-181d and MGMT 3'UTR. The suppressive effect ofmiR-181d on MGMT expression was rescued by the introduction of an MGMT cDNA.Finally, MGMT expression inversely correlated with miR-181d expression inindependent glioblastoma cohorts. Together, these results suggest that miR-181dis a predictive biomarker for TMZ response and that its role is mediated, inpart, by posttranscriptional regulation of MGMT.
PMID: 22570426
Expressiion ProfileDescription: Genome-wide analysis of microRNA expression in surgical specimens of primary glioblastoma multiform
Organism: Homo sapiens
GEO ID: GSE25631
Platform: GPL8179
Number of samples: 87
Design and SampleCancer Type: brain cancer
Cancer SubType: glioblastoma
Cell Line: N/D
Experimental Design: cancer vs normal
Case Sample: glioblastoma
Control Sample: normal brain tissue
Num of Case: 82
Num of Control: 5
Quantification Software: Limma
Num of miRNAs: 857
IdentificationNum of Up: 32
Num of Down: 33