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Site-Specific DNA Demethylation as a Potential Target for Cancer Epigenetic Therapy
Aberrant promoter DNA hypermethylation is a typical characteristic of cancer and it is often seen in malignancies. Recent studies showed that regulatory cis-elements found up-stream of many tumor suppressor gene promoter CpG island (CGI) attract DNA methyltransferases (DNMT) that hypermethylates and...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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SAGE Publications
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8756105/ https://www.ncbi.nlm.nih.gov/pubmed/35036833 http://dx.doi.org/10.1177/2516865720964808 |
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author | Neja, Sultan Abda |
author_facet | Neja, Sultan Abda |
author_sort | Neja, Sultan Abda |
collection | PubMed |
description | Aberrant promoter DNA hypermethylation is a typical characteristic of cancer and it is often seen in malignancies. Recent studies showed that regulatory cis-elements found up-stream of many tumor suppressor gene promoter CpG island (CGI) attract DNA methyltransferases (DNMT) that hypermethylates and silence the genes. As epigenetic alterations are potentially reversible, they make attractive targets for therapeutic intervention. The currently used decitabine (DAC) and azacitidine (AZA) are DNMT inhibitors that follow the passive demethylation pathway. However, they lead to genome-wide demethylation of CpGs in cells, which makes difficult to use it for causal effect analysis and treatment of specific epimutations. Demethylation through specific demethylase enzymes is thus critical for epigenetic resetting of silenced genes and modified chromatins. Yet DNA-binding factors likely play a major role to guide the candidate demethylase enzymes upon its fusion. Before the advent of clustered regulatory interspaced short palindromic repeats (CRISPR), both zinc finger proteins (ZNFs) and transcription activator-like effector protein (TALEs) were used as binding platforms for ten-eleven translocation (TET) enzymes and both systems were able to induce transcription at targeted loci in an in vitro as well as in vivo model. Consequently, the development of site-specific and active demethylation molecular trackers becomes more than hypothetical to makes a big difference in the treatment of cancer in the future. This review is thus to recap the novel albeit distinct studies on the potential use of site-specific demethylation for the development of epigenetic based cancer therapy. |
format | Online Article Text |
id | pubmed-8756105 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-87561052022-01-14 Site-Specific DNA Demethylation as a Potential Target for Cancer Epigenetic Therapy Neja, Sultan Abda Epigenet Insights Review Aberrant promoter DNA hypermethylation is a typical characteristic of cancer and it is often seen in malignancies. Recent studies showed that regulatory cis-elements found up-stream of many tumor suppressor gene promoter CpG island (CGI) attract DNA methyltransferases (DNMT) that hypermethylates and silence the genes. As epigenetic alterations are potentially reversible, they make attractive targets for therapeutic intervention. The currently used decitabine (DAC) and azacitidine (AZA) are DNMT inhibitors that follow the passive demethylation pathway. However, they lead to genome-wide demethylation of CpGs in cells, which makes difficult to use it for causal effect analysis and treatment of specific epimutations. Demethylation through specific demethylase enzymes is thus critical for epigenetic resetting of silenced genes and modified chromatins. Yet DNA-binding factors likely play a major role to guide the candidate demethylase enzymes upon its fusion. Before the advent of clustered regulatory interspaced short palindromic repeats (CRISPR), both zinc finger proteins (ZNFs) and transcription activator-like effector protein (TALEs) were used as binding platforms for ten-eleven translocation (TET) enzymes and both systems were able to induce transcription at targeted loci in an in vitro as well as in vivo model. Consequently, the development of site-specific and active demethylation molecular trackers becomes more than hypothetical to makes a big difference in the treatment of cancer in the future. This review is thus to recap the novel albeit distinct studies on the potential use of site-specific demethylation for the development of epigenetic based cancer therapy. SAGE Publications 2020-10-21 /pmc/articles/PMC8756105/ /pubmed/35036833 http://dx.doi.org/10.1177/2516865720964808 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Review Neja, Sultan Abda Site-Specific DNA Demethylation as a Potential Target for Cancer Epigenetic Therapy |
title | Site-Specific DNA Demethylation as a Potential Target for Cancer Epigenetic Therapy |
title_full | Site-Specific DNA Demethylation as a Potential Target for Cancer Epigenetic Therapy |
title_fullStr | Site-Specific DNA Demethylation as a Potential Target for Cancer Epigenetic Therapy |
title_full_unstemmed | Site-Specific DNA Demethylation as a Potential Target for Cancer Epigenetic Therapy |
title_short | Site-Specific DNA Demethylation as a Potential Target for Cancer Epigenetic Therapy |
title_sort | site-specific dna demethylation as a potential target for cancer epigenetic therapy |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8756105/ https://www.ncbi.nlm.nih.gov/pubmed/35036833 http://dx.doi.org/10.1177/2516865720964808 |
work_keys_str_mv | AT nejasultanabda sitespecificdnademethylationasapotentialtargetforcancerepigenetictherapy |