Epigenetic alterations of CXCL5 in Cr(VI)-induced carcinogenesis.
Epigenetic alterations of CXCL5 in Cr(VI)-induced carcinogenesis.
复制标题
DOI：
10.1016/j.scitotenv.2022.155713
复制
发表时间：
2022-09-10
影响因子：
9.8
通讯作者：
Liu, Ling-Zhi
中科院分区：
文献类型：
--
作者：
Ge, Xin;He, Jun;Wang, Lin;Zhao, Lei;Wang, Yifang;Wu, Gang;Liu, Wenjing;Shu, Yongqian;Gong, Wei;Ma, Xin-Liang;Wang, Yajing;Jiang, Bing-Hua;Liu, Ling-Zhi
长期接触六价铬化合物[Cr(VI)]与癌症风险增加有关，但其分子机制仍有待阐明。在本研究中，我们发现职业接触者外周血单核细胞(PBMC)和血浆中CXCL5水平较非接触者显著升高，且血浆C-X-C基序趋化因子配体5(CXCL5)CXCL5水平与受试者趾甲中铬浓度呈正相关。染铬酸锌小鼠肺组织和外周血单核细胞中CXCL5及其受体CXCR2水平升高。在长期的铬(VI)处理的转化细胞中，CXCL5也明显上调。机制研究表明，CXCL5表达水平的升高受铬(VI)诱导的组蛋白修饰和DNA低甲基化调节，c-Myc/p300复合体是组蛋白H3乙酰化的关键上游调节因子。CXCL5过表达通过上调锌指E盒结合同源异型盒1(ZEB1)促进铬(VI)诱导的上皮向间充质转化(EMT)，从而促进肿瘤的发展。我们的发现确定了一种新的机制，即CXCL5在慢性铬(VI)暴露时上调，并促进EMT和癌症的发生。我们的工作还表明，职业性铬(VI)暴露后外周血单核细胞和血清中CXCL5的mRNA和蛋白水平将升高，这可能是铬(VI)暴露人群癌症预防和健康监测的潜在靶点和生物标志物。
Chronic exposure to hexavalent chromium compounds [Cr(VI)] is associated with an increased risk of cancers, but the molecular mechanisms remain to be elucidated. In this study, we found that CXCL5 levels in peripheral blood monocytes (PBMCs) and plasma from workers with occupational exposure to Cr(VI) were dramatically upregulated compared to non-exposure healthy subjects, and plasma C-X-C Motif Chemokine Ligand 5 (CXCL5) CXCL5 levels were positively correlated with Cr concentrations in subjects’ toenails. Zinc chromate exposed mice showed higher levels of CXCL5 and its receptor CXCR2 in lung tissues, and in PBMCs. Similar CXCL5 upregulation was evident in Cr(VI)-induced transformed (Cr-T) cells with long-term Cr(VI) treatment. Mechanistic studies showed that elevated CXCL5 expression levels were regulated by Cr(VI)-induced histone modifications and DNA hypomethylation, and that the c-Myc/p300 complex was a key upstream regulator of histone H3 acetylation. CXCL5 overexpression promoted Cr (VI)-induced the epithelial to mesenchyme transition (EMT) by upregulating zinc finger E-box binding homeobox 1 (ZEB1) to promote tumor development. Our findings identify a novel mechanism by which CXCL5 is upregulated and promotes EMT and carcinogenesis upon chronic Cr(VI) exposure. Our work also implies that CXCL5 mRNA and protein levels will elevate in PBMCs and serum after occupational Cr(VI) exposure, which may be a potential target and biomarker for cancer prevention and health surveillance among populations exposed to Cr(VI).
登录
查看更多内容
DNA 甲基化在 Cr (VI) 诱导的两种细胞系细胞周期停滞中的作用。
影响因子：
3.7
作者：
Lou J;Wang Y;Yao C;Jin L;Wang X;Xiao Y;Wu N;Song P;Song Y;Tan Y;Gao M;Liu K;Zhang X
通讯作者：
Zhang X
DOI：
10.1083/jcb.134.4.971
发表时间：
1996-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Goldman RD;Khuon S;Chou YH;Opal P;Steinert PM
通讯作者：
Steinert PM
影响因子：
5
作者：
O'Brien, Katie M.;White, Alexandra J.;Weinberg, Clarice R.
通讯作者：
Weinberg, Clarice R.
影响因子：
15.9
作者：
Arenberg, DA;Keane, MP;Strieter, RM
通讯作者：
Strieter, RM
影响因子：
11.5
作者：
Nakajima, S;Doi, R;Imamura, M
通讯作者：
Imamura, M