Related Experiment Video
Updated: May 22, 2026
Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
miR-181d: a predictive glioblastoma biomarker that downregulates MGMT expression
Wei Zhang1, Jing Zhang, Katherine Hoadley
1Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, China.
Abstract:
Genome-wide microRNA (miRNA) profiling of 82 glioblastomas demonstrated that miR-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 independent cohorts, an association of miR-181d with survival was evident in patients who underwent TMZ treatment but was not observed in patients without TMZ therapy. Bioinformatic analysis of potential genes regulated by miR-181d revealed methyl-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 a direct interaction between miR-181d and MGMT 3'UTR. The suppressive effect of miR-181d on MGMT expression was rescued by the introduction of an MGMT cDNA. Finally, MGMT expression inversely correlated with miR-181d expression in independent glioblastoma cohorts. Together, these results suggest that miR-181d is a predictive biomarker for TMZ response and that its role is mediated, in part, by posttranscriptional regulation of MGMT.
Insights
MicroRNA-181d (miR-181d) predicts glioblastoma patient survival, especially with temozolomide (TMZ) treatment. It functions by downregulating MGMT, a key DNA repair enzyme, impacting treatment response.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Glioblastoma is an aggressive brain tumor with poor prognosis.
- Identifying biomarkers for treatment response is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the role of microRNA-181d (miR-181d) as a potential biomarker for glioblastoma patient survival and response to temozolomide (TMZ).
- To elucidate the molecular mechanism by which miR-181d influences glioblastoma progression, focusing on its interaction with MGMT.
Main Methods:
- Genome-wide miRNA profiling in glioblastoma patient samples.
- Validation of miR-181d association with survival in independent cohorts (TCGA and a separate cohort).
- Bioinformatic analysis to identify miR-181d targets, followed by experimental validation including gene expression analysis, luciferase reporter assays, and co-precipitation studies.
Main Results:
- miR-181d expression was inversely associated with overall survival in glioblastoma patients, particularly those treated with TMZ.
- miR-181d directly targets and downregulates methyl-guanine-methyl-transferase (MGMT) mRNA and protein expression.
- MGMT expression was found to be inversely correlated with miR-181d levels in glioblastoma tissues.
Conclusions:
- miR-181d serves as a predictive biomarker for TMZ treatment response in glioblastoma.
- The predictive role of miR-181d is mediated, at least in part, through the posttranscriptional regulation of MGMT.
Related Concept Videos
01:22MicroRNAs
01:22MicroRNAs