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Nicotinamide N-Methyltransferase: An Emerging Protagonist in Cancer Macro(r)evolution
Biomolecules, Volume: 11, Issue: 10, Start page: 1418
Swansea University Author: Paul Facey
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Copyright: © 2021 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license
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DOI (Published version): 10.3390/biom11101418
Abstract
Nicotinamide N-methyltransferase (NNMT) has progressed from being considered merely a Phase II metabolic enzyme to one with a central role in cell function and energy metabolism. Over the last three decades, a significant body of evidence has accumulated which clearly demonstrates a central role for...
Published in: | Biomolecules |
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ISSN: | 2218-273X |
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MDPI AG
2021
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URI: | https://cronfa.swan.ac.uk/Record/cronfa58145 |
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2021-10-25T15:13:19.1198981 v2 58145 2021-09-29 Nicotinamide N-Methyltransferase: An Emerging Protagonist in Cancer Macro(r)evolution dc25910b8004b2694df68ed7426e1286 0000-0002-3229-0255 Paul Facey Paul Facey true false 2021-09-29 BMS Nicotinamide N-methyltransferase (NNMT) has progressed from being considered merely a Phase II metabolic enzyme to one with a central role in cell function and energy metabolism. Over the last three decades, a significant body of evidence has accumulated which clearly demonstrates a central role for NNMT in cancer survival, metastasis, and drug resistance. In this review, we discuss the evidence supporting a role for NNMT in the progression of the cancer phenotype and how it achieves this by driving the activity of pro-oncogenic NAD+-consuming enzymes. We also describe how increased NNMT activity supports the Warburg effect and how it promotes oncogenic changes in gene expression. We discuss the regulation of NNMT activity in cancer cells by both post-translational modification of the enzyme and transcription factor binding to the NNMT gene, and describe for the first time three long non-coding RNAs which may play a role in the regulation of NNMT transcription. We complete the review by discussing the development of novel anti-cancer therapeutics which target NNMT and provide insight into how NNMT-based therapies may be best employed clinically. Journal Article Biomolecules 11 10 1418 MDPI AG 2218-273X oncogenesis; methylation; tumorigenesis; drug resistance; cancer stem cell; Warburg effect; transcription factors; NAD+ 28 9 2021 2021-09-28 10.3390/biom11101418 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2021-10-25T15:13:19.1198981 2021-09-29T14:10:01.0894551 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Richard B. Parsons 1 Paul Facey 0000-0002-3229-0255 2 58145__21290__bab61332f0f94bf3b029a47e20aa9c64.pdf 58145.pdf 2021-10-25T15:07:33.5370963 Output 2660401 application/pdf Version of Record true Copyright: © 2021 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license true eng https://creativecommons.org/licenses/by/4.0/ |
title |
Nicotinamide N-Methyltransferase: An Emerging Protagonist in Cancer Macro(r)evolution |
spellingShingle |
Nicotinamide N-Methyltransferase: An Emerging Protagonist in Cancer Macro(r)evolution Paul Facey |
title_short |
Nicotinamide N-Methyltransferase: An Emerging Protagonist in Cancer Macro(r)evolution |
title_full |
Nicotinamide N-Methyltransferase: An Emerging Protagonist in Cancer Macro(r)evolution |
title_fullStr |
Nicotinamide N-Methyltransferase: An Emerging Protagonist in Cancer Macro(r)evolution |
title_full_unstemmed |
Nicotinamide N-Methyltransferase: An Emerging Protagonist in Cancer Macro(r)evolution |
title_sort |
Nicotinamide N-Methyltransferase: An Emerging Protagonist in Cancer Macro(r)evolution |
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dc25910b8004b2694df68ed7426e1286 |
author_id_fullname_str_mv |
dc25910b8004b2694df68ed7426e1286_***_Paul Facey |
author |
Paul Facey |
author2 |
Richard B. Parsons Paul Facey |
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Biomolecules |
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2021 |
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Swansea University |
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2218-273X |
doi_str_mv |
10.3390/biom11101418 |
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MDPI AG |
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Faculty of Medicine, Health and Life Sciences |
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Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine |
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description |
Nicotinamide N-methyltransferase (NNMT) has progressed from being considered merely a Phase II metabolic enzyme to one with a central role in cell function and energy metabolism. Over the last three decades, a significant body of evidence has accumulated which clearly demonstrates a central role for NNMT in cancer survival, metastasis, and drug resistance. In this review, we discuss the evidence supporting a role for NNMT in the progression of the cancer phenotype and how it achieves this by driving the activity of pro-oncogenic NAD+-consuming enzymes. We also describe how increased NNMT activity supports the Warburg effect and how it promotes oncogenic changes in gene expression. We discuss the regulation of NNMT activity in cancer cells by both post-translational modification of the enzyme and transcription factor binding to the NNMT gene, and describe for the first time three long non-coding RNAs which may play a role in the regulation of NNMT transcription. We complete the review by discussing the development of novel anti-cancer therapeutics which target NNMT and provide insight into how NNMT-based therapies may be best employed clinically. |
published_date |
2021-09-28T04:14:26Z |
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11.03559 |