| Autor: |
Kang, Yu‐Ting1,2 (AUTHOR), Yang, Wan‐Jung1,3 (AUTHOR), Huang, Hsu Chih1,4 (AUTHOR), Tang, Sheau‐Chung5 (AUTHOR) s6160051@nutc.edu.tw, Ko, Jiunn‐Liang1,6 (AUTHOR) jlko@csmu.edu.tw |
| Předmět: |
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| Zdroj: |
Environmental Toxicology. Mar2024, Vol. 39 Issue 3, p1729-1736. 8p. |
| Abstrakt: |
Nickel (Ni) is a human carcinogen with genotoxic and epigenotoxic effects. Environmental and occupational exposure to Ni increases the risk of cancer and chronic inflammatory diseases. Our previous findings indicate that Ni alters gene expression through epigenetic regulation, specifically impacting E‐cadherin and angiopoietin‐like 4 (ANGPTL4), involved in epithelial‐mesenchymal transition and migration. GST‐M2, a member of the glutathione S‐transferase (GST) enzyme family, plays a crucial role in cellular defense against oxidative damage and has been increasingly associated with cancer. GST‐M2 overexpression inhibits lung cancer invasion and metastasis in vitro and in vivo. Hypermethylation of its promoter in cancer cells reduces gene expression, correlating with poor prognosis in non‐small‐cell lung cancer patients. The impact of Ni on GST‐M2 remains unclear. We will investigate whether nickel exerts regulatory effects on GST‐M2 through epigenetic modifications. Additionally, metformin, an antidiabetic drug, is being studied as a chemopreventive agent against nickel‐induced damage. Our findings indicate that nickel chloride (NiCl2) exposure, both short‐term and long‐term, represses GST‐M2 expression. However, the expression can be restored by demethylation agent 5‐aza‐2′‐deoxycytidine and metformin. NiCl2 promotes hypermethylation of the GST‐M2 promoter, as confirmed by methylation‐specific PCR and bisulfite sequencing. Additionally, NiCl2 also influences histone acetylation, and metformin counteracts the suppressive effect of NiCl2 on histone H3 expression. Metformin reestablishes the binding of specificity protein 1 to the GST‐M2 promoter, which is otherwise disrupted by NiCl2. These findings elucidate the mechanism by which Ni reduces GST‐M2 expression and transcriptional activity, potentially contributing to Ni‐induced lung carcinogenesis. [ABSTRACT FROM AUTHOR] |
| Databáze: |
GreenFILE |
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