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Updated: Jul 25, 2025
Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
A Comprehensive Review of miRNAs and Their Epigenetic Effects in Glioblastoma
Hera Hasan1, Mohammad Afzal2, Javier S Castresana3
1Interdisciplinary Brain Research Centre, Faculty of Medicine, Aligarh Muslim University, Aligarh 202002, India.
Abstract:
Glioblastoma is the most aggressive form of brain tumor originating from glial cells with a maximum life expectancy of 14.6 months. Despite the establishment of multiple promising therapies, the clinical outcome of glioblastoma patients is abysmal. Drug resistance has been identified as a major factor contributing to the failure of current multimodal therapy. Epigenetic modification, especially DNA methylation has been identified as a major regulatory mechanism behind glioblastoma progression. In addition, miRNAs, a class of non-coding RNA, have been found to play a role in the regulation as well as in the diagnosis of glioblastoma. The relationship between epigenetics, drug resistance, and glioblastoma progression has been clearly demonstrated. MGMT hypermethylation, leading to a lack of MGMT expression, is associated with a cytotoxic effect of TMZ in GBM, while resistance to TMZ frequently appears in MGMT non-methylated GBM. In this review, we will elaborate on known miRNAs linked to glioblastoma; their distinctive oncogenic or tumor suppressor roles; and how epigenetic modification of miRNAs, particularly via methylation, leads to their upregulation or downregulation in glioblastoma. Moreover, we will try to identify those miRNAs that might be potential regulators of MGMT expression and their role as predictors of tumor response to temozolomide treatment. Although we do not impact clinical data and survival, we open possible experimental approaches to treat GBM, although they should be further validated with clinically oriented studies.
Insights
Glioblastoma (GBM) drug resistance is linked to epigenetic changes. MicroRNAs (miRNAs) are implicated in GBM progression and may predict response to temozolomide (TMZ) therapy by regulating MGMT expression.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Epigenetics
Background:
- Glioblastoma (GBM) is an aggressive brain tumor with poor prognosis, often failing current therapies due to drug resistance.
- Epigenetic modifications, particularly DNA methylation, are key drivers of GBM progression and therapeutic resistance.
- MicroRNAs (miRNAs), small non-coding RNAs, are involved in GBM regulation and diagnosis, with their epigenetic alterations impacting tumor behavior.
Purpose of the Study:
- To review known miRNAs associated with glioblastoma and their oncogenic or tumor suppressor functions.
- To explore how epigenetic modifications, specifically methylation, influence miRNA expression in glioblastoma.
- To identify potential miRNAs regulating MGMT expression and predicting temozolomide (TMZ) treatment response in GBM.
Main Methods:
- Literature review focusing on glioblastoma, epigenetic modifications (DNA methylation), miRNAs, MGMT, and temozolomide (TMZ) resistance.
- Analysis of the interplay between miRNA epigenetic regulation and their roles in glioblastoma pathogenesis.
- Identification of miRNAs potentially modulating MGMT expression and their predictive value for TMZ efficacy.
Main Results:
- MGMT hypermethylation correlates with TMZ sensitivity, while its absence is linked to resistance in glioblastoma.
- Epigenetic dysregulation of miRNAs contributes to glioblastoma progression, with specific miRNAs exhibiting oncogenic or tumor suppressor roles.
- Certain miRNAs may serve as crucial regulators of MGMT expression, influencing glioblastoma response to temozolomide.
Conclusions:
- Understanding miRNA epigenetic regulation in glioblastoma is critical for deciphering drug resistance mechanisms.
- miRNAs hold potential as biomarkers for predicting glioblastoma response to temozolomide therapy.
- Targeting miRNA epigenetic modifications offers novel therapeutic strategies for glioblastoma, requiring further clinical validation.
