A Comprehensive Review of miRNAs and Their Epigenetic Effects in Glioblastoma
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 fact...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/12/1578 |
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| author | Hera Hasan Mohammad Afzal Javier S. Castresana Mehdi H. Shahi |
| author_facet | Hera Hasan Mohammad Afzal Javier S. Castresana Mehdi H. Shahi |
| author_sort | Hera Hasan |
| collection | DOAJ |
| description | 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. <i>MGMT</i> hypermethylation, leading to a lack of <i>MGMT</i> expression, is associated with a cytotoxic effect of TMZ in GBM, while resistance to TMZ frequently appears in <i>MGMT</i> 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 <i>MGMT</i> 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. |
| first_indexed | 2024-03-11T02:38:57Z |
| format | Article |
| id | doaj.art-87dc65131cdb45e4ab6993db75e40bd9 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T02:38:57Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-87dc65131cdb45e4ab6993db75e40bd92023-11-18T09:42:58ZengMDPI AGCells2073-44092023-06-011212157810.3390/cells12121578A Comprehensive Review of miRNAs and Their Epigenetic Effects in GlioblastomaHera Hasan0Mohammad Afzal1Javier S. Castresana2Mehdi H. Shahi3Interdisciplinary Brain Research Centre, Faculty of Medicine, Aligarh Muslim University, Aligarh 202002, IndiaDepartment of Zoology, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, IndiaDepartment of Biochemistry and Genetics, University of Navarra School of Sciences, 31008 Pamplona, SpainInterdisciplinary Brain Research Centre, Faculty of Medicine, Aligarh Muslim University, Aligarh 202002, IndiaGlioblastoma 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. <i>MGMT</i> hypermethylation, leading to a lack of <i>MGMT</i> expression, is associated with a cytotoxic effect of TMZ in GBM, while resistance to TMZ frequently appears in <i>MGMT</i> 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 <i>MGMT</i> 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.https://www.mdpi.com/2073-4409/12/12/1578glioblastomamiRNAtemozolomideepigeneticsDNA methylation |
| spellingShingle | Hera Hasan Mohammad Afzal Javier S. Castresana Mehdi H. Shahi A Comprehensive Review of miRNAs and Their Epigenetic Effects in Glioblastoma Cells glioblastoma miRNA temozolomide epigenetics DNA methylation |
| title | A Comprehensive Review of miRNAs and Their Epigenetic Effects in Glioblastoma |
| title_full | A Comprehensive Review of miRNAs and Their Epigenetic Effects in Glioblastoma |
| title_fullStr | A Comprehensive Review of miRNAs and Their Epigenetic Effects in Glioblastoma |
| title_full_unstemmed | A Comprehensive Review of miRNAs and Their Epigenetic Effects in Glioblastoma |
| title_short | A Comprehensive Review of miRNAs and Their Epigenetic Effects in Glioblastoma |
| title_sort | comprehensive review of mirnas and their epigenetic effects in glioblastoma |
| topic | glioblastoma miRNA temozolomide epigenetics DNA methylation |
| url | https://www.mdpi.com/2073-4409/12/12/1578 |
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