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Nicotinamide N-Methyltransferase: A Promising Biomarker and Target for Human Cancer Therapy
Xiao-Yu Li1, Ya-Nan Pi2, Yao Chen3
1The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Abstract:
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 N-methyltransferase (NNMT) is a metabolic enzyme involved in controlling methylation potential, impacting DNA and histone epigenetic modification. NNMT overexpression has been described in various solid cancer tissues and even body fluids, including serum, urine, and saliva. Furthermore, accumulating evidence has shown that NNMT 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.
Insights
Nicotinamide N-methyltransferase (NNMT) is crucial in cancer development and drug resistance. Targeting NNMT offers a promising strategy for novel cancer therapies and diagnostics.
Area of Science:
- Oncology
- Epigenetics
- Metabolic pathways
Background:
- Cancer cells utilize metabolic plasticity and epigenetic remodeling for uncontrolled proliferation.
- The metabolic-epigenetic axis is a key area in cancer research, offering personalized treatment avenues.
- Nicotinamide N-methyltransferase (NNMT) is an enzyme regulating methylation potential, affecting DNA and histone modifications.
Purpose of the Study:
- To review NNMT's role in cancer.
- To evaluate NNMT as a diagnostic biomarker and therapeutic target.
- To elucidate NNMT's mechanisms in epigenetics and inhibitor development.
Main Methods:
- Literature review on NNMT's function in carcinogenesis.
- Analysis of NNMT overexpression in various cancer types and body fluids.
- Examination of NNMT knockdown effects on tumorigenesis and chemoresistance.
- Investigation of NNMT inhibitors, such as yuanhuadine, in reversing drug resistance.
Main Results:
- NNMT overexpression is prevalent in solid tumors and detectable in bodily fluids.
- NNMT knockdown reduces cancer cell proliferation, tumorigenesis, and chemoresistance.
- NNMT inhibition, exemplified by yuanhuadine, can overcome drug resistance in lung cancer.
Conclusions:
- NNMT presents a viable target for developing innovative anticancer treatments.
- NNMT holds potential as a diagnostic biomarker for various cancers.
- Further research into NNMT's epigenetic mechanisms and selective inhibitors is warranted for effective cancer therapy.
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