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Nicotinamide N-Methyltransferase: An Emerging Protagonist in Cancer Macro(r)evolution

Richard B. Parsons, Paul Facey Orcid Logo

Biomolecules, Volume: 11, Issue: 10, Start page: 1418

Swansea University Author: Paul Facey Orcid Logo

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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...

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Published in: Biomolecules
ISSN: 2218-273X
Published: MDPI AG 2021
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URI: https://cronfa.swan.ac.uk/Record/cronfa58145
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first_indexed 2021-10-25T14:08:20Z
last_indexed 2021-10-26T03:24:21Z
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spelling 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
author_id_str_mv dc25910b8004b2694df68ed7426e1286
author_id_fullname_str_mv dc25910b8004b2694df68ed7426e1286_***_Paul Facey
author Paul Facey
author2 Richard B. Parsons
Paul Facey
format Journal article
container_title Biomolecules
container_volume 11
container_issue 10
container_start_page 1418
publishDate 2021
institution Swansea University
issn 2218-273X
doi_str_mv 10.3390/biom11101418
publisher MDPI AG
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
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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score 11.016235

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