Abstract
Arsenic is a known human carcinogen. Low doses of arsenic can induce cell proliferation, but the mechanism remains elusive. Aerobic glycolysis, also known as the Warburg effect, is one of the characteristics of tumour cells and rapidly proliferating cells. P53 is a tumour suppressor gene that has been shown to be a negative regulator of aerobic glycolysis. SIRT1 is a deacetylase that inhibits the function of P53. In this study, we found that P53 was involved in low dose of arsenic-induced aerobic glycolysis through regulating HK2 expression in L-02 cells. Moreover, SIRT1 not only inhibited P53 expression but also decreased the acetylation level of P53-K382 in arsenic-treated L-02 cells. Meanwhile, SIRT1 influenced the expression of HK2 and LDHA, which then promoted arsenic-induced glycolysis in L-02 cells. Therefore, our study demonstrated that the SIRT1/P53 pathway is involved in arsenic-induced glycolysis, thereby promoting cell proliferation, which provides theoretical basis for enriching the mechanism of arsenic carcinogenesis.
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Acknowledgements
This work was supported by the Natural Science Foundation of China (Grant No.81673109 and Grant No.81830099).
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This work was supported by the Natural Science Foundation of China (Grant No.81673109 and Grant No.81830099).
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Meichen Zhang: Methodology, Visualization, Data curation, Writing-original draft. Zaihong Zhang: Methodology Visualization, Investigation, Data curation, Writing—review & editing. Fanshuo Yin: Investigation. Qun Lou: Investigation, Methodology. Xin Zhang: Investigation. Yunyi Yin: Investigation. Haili Xu: Investigation. Ying Zhang: Investigation. Chenlu Fan: Investigation. Yanhui Gao: Conceptualization, Project administration, Supervision, Resources. Yanmei Yang: Conceptualization, Writing—review & editing, Project administration, Supervision.
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Supplementary file2 Fig.S1 Overexpression P53 by P53 plasmid, a-c L-02 cells were transfected with plasmid of P53 or pcDNA and then treated with or without 0.2 μmol/L iAs3+ for another 48 h. a Real-time qPCR analysis was used to detect the expression of P53 mRNA. b-c The expression of P53 protein was evaluated with western blot. Data are expressed as mean ± SD (n = 3). “*” indicates statistically significant difference, compared with the control group (* P < 0.05 and ** P < 0.01). Fig.S2 SIRT1 expression was knockdown by SIRT1 siRNA, a-c L-02 cells were transfected with SIRT1 siRNA of or negative control and then treated with or without 0.2 μmol/L iAs3+ for another 48 h. a Real-time qPCR analysis was used to detect the expression of SIRT1 mRNA. b-c The expression of SIRT1 protein was evaluated with western blot. Data are expressed as mean ± SD (n = 3). “*” indicates statistically significant difference, compared with the control group (* P < 0.05 and ** P < 0.01). (PDF 533 KB)
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Zhang, M., Zhang, Z., Lou, Q. et al. SIRT1/P53 pathway is involved in the Arsenic induced aerobic glycolysis in hepatocytes L-02 cells. Environ Sci Pollut Res 30, 73799–73811 (2023). https://doi.org/10.1007/s11356-023-27570-5
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DOI: https://doi.org/10.1007/s11356-023-27570-5