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Updated: May 12, 2026
Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
MiR-139 inhibits Mcl-1 expression and potentiates TMZ-induced apoptosis in glioma
Rui-Yan Li1, Ling-Chao Chen, Hai-Yan Zhang
1Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Aims:
Mcl-1, an antiapoptotic member of the Bcl-2 family, is overexpressed in human glioblastoma, conferring a survival advantage to tumor cells. The mechanisms underlying its dysregulation have not been clarified. In this study, we explored the involvement of micro-RNAs that acted as endogenous sequence-specific suppressors of gene expression.
Methods And Results:
Using computational and TCGA analysis, we identified miR-139 as being downregulated in glioblastoma in comparison with human brain tissue, as well as possessing a putative target site in Mcl-1 mRNA. Overexpression of miR-139 led to a clear decrease in Mcl-1 expression in gliomas. Reporter assays revealed direct post-transcriptional regulation involving miR-139 and the 3'-untranslated region of Mcl-1. Human glioma tissues with low expression of miR-139 displayed higher expression of Mcl-1 protein than those with high expression, suggesting that low miR-139 contributes to Mcl-1 overexpression. In addition, upregulation of miR-139 suppressed the proliferation and enhanced temozolomide (TMZ)-induced apoptosis. Finally, we observed that Mcl-1 knockdown resulted in similar effects compared with miR-139 transfection.
Conclusion:
Our results suggested that miR-139 negatively regulated Mcl-1 and induced apoptosis in cooperation with an anticancer drug TMZ in glioma.
Insights
MicroRNA-139 (miR-139) is downregulated in glioblastoma, leading to increased Mcl-1 expression. Restoring miR-139 suppresses tumor growth and enhances chemotherapy-induced apoptosis.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Mcl-1 is overexpressed in glioblastoma, promoting tumor cell survival.
- Mechanisms of Mcl-1 dysregulation in glioblastoma are not fully understood.
- MicroRNAs (miRNAs) are key regulators of gene expression.
Purpose of the Study:
- To investigate the role of miRNAs in regulating Mcl-1 expression in glioblastoma.
- To identify specific miRNAs targeting Mcl-1 mRNA.
- To explore the therapeutic potential of miRNA-based strategies in glioblastoma.
Main Methods:
- Computational analysis and TCGA data mining to identify potential miRNA targets.
- In vitro experiments including miRNA overexpression, reporter assays, and Western blotting.
- Analysis of human glioma tissues to correlate miRNA and protein expression.
- Assessment of cell proliferation and apoptosis induction.
Main Results:
- miR-139 was found to be downregulated in glioblastoma.
- miR-139 directly targets Mcl-1 mRNA, reducing its expression.
- Low miR-139 levels correlate with high Mcl-1 protein expression in glioma tissues.
- Upregulation of miR-139 inhibited glioma cell proliferation and enhanced temozolomide-induced apoptosis.
- Mcl-1 knockdown mimicked the effects of miR-139 upregulation.
Conclusions:
- miR-139 acts as a tumor suppressor in glioblastoma by negatively regulating Mcl-1.
- miR-139 enhances the efficacy of temozolomide in inducing apoptosis in glioma cells.
- Restoring miR-139 levels represents a potential therapeutic strategy for glioblastoma.
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