Nicotinamide N-Methyltransferase Suppression Participates in Nickel-Induced Histone H3 Lysine9 Dimethylation in BEAS-2B Cells

Li, Qian; He, Mindi; Mao, Lin; Wang, Xue; Jiang, Yulin; Li, Min; Lu, Yonghui; Yu, Zhengping; Zhou, Zhou

doi:10.1159/000475432

Cited by 7 publications

(4 citation statements)

References 39 publications

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“…NNMT catalyzes the methylation of nicotinamide and pyridine, therefore regulating the metabolism of drugs and other xenobiotics (21). The abnormal expression of NNMT has been widely identified in several types of tumor (22,23).…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide N-methyltransferase promotes epithelial-mesenchymal transition in gastric cancer cells by activating transforming growth factor-β1 expression

et al. 2018

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Abstract. Previous studies have demonstrated that nicotinamide N-methyltransferase (NNMT) is aberrantly expressed in a number of tumors. In the present study, it was demonstrated that the gene and protein levels of NNMT were significantly increased in gastric cancer cells. Furthermore, upregulation of NNMT significantly increased the expression of mesenchymal markers, including α-smooth muscle actin (SMA), vimentin and fibronectin, but decreased the levels of epithelial cadherin. Since transforming growth factor (TGF)-β1 may serve a key function in epithelial-mesenchymal transition (EMT), the effects of NNMT on the expression of TGF-β1 were investigated in BGC-823 cells. The results demonstrated that overexpression of NNMT significantly induced the expression of TGF-β1. However, knockdown of NNMT inhibited the expression of TGF-β1, mothers against decapentaplegic homolog (Smad)2 and α-SMA. Additionally, pre-incubation with TGF-β1 partially eliminated NNMT-mediated changes in EMT. Collectively, the results demonstrated that upregulation of NNMT in gastric cancer cells may increase the expression of TGF-β1, therefore activating TGF-β1/Smad signaling, which in turn promotes EMT.

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Section: Discussionmentioning

confidence: 99%

Nicotinamide N-methyltransferase promotes epithelial-mesenchymal transition in gastric cancer cells by activating transforming growth factor-β1 expression

et al. 2018

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“…proposed that 1-MNA is a methylation sink ( 88 ). NNMT-mediated SAM depletion can alter cell MP, contributing to the change in global epigenetic histone profiles in cancer ( 7 , 93 ). For example, NNMT can alter H2K27 methylation status, affecting m6A of CD44, consequently contributing to the formation of CD44v3, which is closely related to tumor metastasis ( 39 ).…”

Section: The Crosstalk Between Tumor Metabolism and Epigeneticsmentioning

confidence: 99%

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

Chen

et al. 2022

Front. Oncol.

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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. NicotinamideN-methyltransferase (NNMT) is a metabolic enzyme involved in controlling methylation potential, impacting DNA and histone epigenetic modification.NNMToverexpression has been described in various solid cancer tissues and even body fluids, including serum, urine, and saliva. Furthermore, accumulating evidence has shown thatNNMTknockdown 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.

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“…Nicotinamide N-methyltransferase (NNMT) has been shown to decrease histone methylation by decreasing the cellular S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio [ 126 ]. Ni has been shown to induce H3K9me2 by inhibiting NNMT expression to increase the cellular SAM/SAH ratio [ 127 ].…”

Section: Nickel (Ni)mentioning

confidence: 99%

Epigenetic Regulation in Chromium-, Nickel- and Cadmium-Induced Carcinogenesis

Zhao

Islam

Wang

et al. 2022

Cancers

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Environmental and occupational exposure to heavy metals, such as hexavalent chromium, nickel, and cadmium, are major health concerns worldwide. Some heavy metals are well-documented human carcinogens. Multiple mechanisms, including DNA damage, dysregulated gene expression, and aberrant cancer-related signaling, have been shown to contribute to metal-induced carcinogenesis. However, the molecular mechanisms accounting for heavy metal-induced carcinogenesis and angiogenesis are still not fully understood. In recent years, an increasing number of studies have indicated that in addition to genotoxicity and genetic mutations, epigenetic mechanisms play critical roles in metal-induced cancers. Epigenetics refers to the reversible modification of genomes without changing DNA sequences; epigenetic modifications generally involve DNA methylation, histone modification, chromatin remodeling, and non-coding RNAs. Epigenetic regulation is essential for maintaining normal gene expression patterns; the disruption of epigenetic modifications may lead to altered cellular function and even malignant transformation. Therefore, aberrant epigenetic modifications are widely involved in metal-induced cancer formation, development, and angiogenesis. Notably, the role of epigenetic mechanisms in heavy metal-induced carcinogenesis and angiogenesis remains largely unknown, and further studies are urgently required. In this review, we highlight the current advances in understanding the roles of epigenetic mechanisms in heavy metal-induced carcinogenesis, cancer progression, and angiogenesis.

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Nicotinamide N-Methyltransferase Suppression Participates in Nickel-Induced Histone H3 Lysine9 Dimethylation in BEAS-2B Cells

Cited by 7 publications

References 39 publications

Nicotinamide N-methyltransferase promotes epithelial-mesenchymal transition in gastric cancer cells by activating transforming growth factor-β1 expression

Nicotinamide N-methyltransferase promotes epithelial-mesenchymal transition in gastric cancer cells by activating transforming growth factor-β1 expression

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

Epigenetic Regulation in Chromium-, Nickel- and Cadmium-Induced Carcinogenesis

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