Perspective

Nicotinamide N-methyl transferase and cancer-associated thrombosis: insights to prevention and management

https://orcid.org/0000-0002-1143-9161

Department of Molecular, Cell & Systems Biology, University of California, Riverside, CA 92521, USA

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Marzieh Roayaei Ardakany

Department of Dermatology, Imam Khomeini Hospital, Jondishapour University of Medical Science, Ahvaz, Iran

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Saied Ebrahimi

Research Department of Rajaei Heart Center, Iran University of Medical Sciences, Tehran, Iran

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Nima Rezaei

*Author for correspondence: Tel.: +98 21 6692 9234;

E-mail Address: rezaei_nima@tums.ac.ir

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E-mail Address: rezaei_nima@yahoo.com

Research Center for Immunodeficiency, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

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Published Online:22 May 2023https://doi.org/10.2217/epi-2023-0078

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Abstract

Nicotinamide metabolism is important in carcinogenesis. Nicotinamide affects the cellular methyl pool, thus affecting DNA and histone methylation and gene expression. Cancer cells have increased expression of nicotinamide N-methyl transferase (NNMT), the key enzyme in nicotinamide metabolism. NNMT contributes to tumor angiogenesis. Overexpression of NNMT is associated with poorer prognosis in cancers. Additionally, NNMT can contribute to cancer-associated morbidities, such as cancer-associated thrombosis. 1-methylnicotinamide (1-MNA), a metabolite of nicotinamide, has anti-inflammatory and antithrombotic effects. Therefore, targeting NNMT can affect both carcinogenesis and cancer-associated morbidities. Several antitumor drugs have been shown to inhibit NNMT expression in cancer cells. Implementing these drugs to reverse NNMT effects in addition to 1-MNA supplementation has the potential to prevent cancer-associated thrombosis through various mechanisms.

Graphical abstract

The yin and yang of NNMT activity. Nicotinamide and 1-MNA have anticancer and anti-inflammatory properties. Increased activity of NNMT will lead to excretion of nicotinamide and 1-MNA. In the process of metabolizing nicotinamide, homocysteine is produced, which has thrombotic properties.

Keywords:

Papers of special note have been highlighted as: • of interest

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Received 1 March 2023

Accepted 24 February 2023

Published online 22 May 2023

Published in print March 2023

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The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

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