AUTHOR=Li Xiao-Yu , Pi Ya-Nan , Chen Yao , Zhu Qi , Xia Bai-Rong 

TITLE=Nicotinamide N-Methyltransferase: A Promising Biomarker and Target for Human Cancer Therapy

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.894744

DOI=10.3389/fonc.2022.894744

ISSN=2234-943X

ABSTRACT=<p>Cancer cells typically exhibit a tightly regulated program of metabolic plasticity and epigenetic remodeling to meet the demand of uncontrolled cell proliferation. The metabolic–epigenetic axis has recently become an increasingly hot topic in carcinogenesis and offers new avenues for innovative and personalized cancer treatment strategies. Nicotinamide <italic>N</italic>-methyltransferase (NNMT) is a metabolic enzyme involved in controlling methylation potential, impacting DNA and histone epigenetic modification. <italic>NNMT</italic> overexpression has been described in various solid cancer tissues and even body fluids, including serum, urine, and saliva. Furthermore, accumulating evidence has shown that <italic>NNMT</italic> knockdown significantly decreases tumorigenesis and chemoresistance capacity. Most importantly, the natural NNMT inhibitor yuanhuadine can reverse epidermal growth factor receptor tyrosine kinase inhibitor resistance in lung cancer cells. In this review, we evaluate the possibility of NNMT as a diagnostic biomarker and molecular target for effective anticancer treatment. We also reveal the exact mechanisms of how NNMT affects epigenetics and the development of more potent and selective inhibitors.</p>