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Poly( ADP ‐ribose) glycohydrolase silencing‐mediated H2B expression inhibits benzo(a)pyrene‐induced carcinogenesis
Environmental Toxicology ( IF 4.4 ) Pub Date : 2020-10-12 , DOI: 10.1002/tox.23034 Zhuoying Zeng 1, 2 , Jingjing Lu 3 , Desheng Wu 4 , Ran Zuo 3 , Yuxi Li 3, 5 , Haiyan Huang 4 , Jianhui Yuan 3 , Zhangli Hu 1, 2
Environmental Toxicology ( IF 4.4 ) Pub Date : 2020-10-12 , DOI: 10.1002/tox.23034 Zhuoying Zeng 1, 2 , Jingjing Lu 3 , Desheng Wu 4 , Ran Zuo 3 , Yuxi Li 3, 5 , Haiyan Huang 4 , Jianhui Yuan 3 , Zhangli Hu 1, 2
Affiliation
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Poly(ADP-ribose) glycohydrolase (PARG) as a main enzyme hydrolyzing poly(ADP-ribose) in eukaryotes, and its silencing can inhibit benzo(a)pyrene (BaP)-induced carcinogenesis. A thorough understanding of the mechanism of PARG silenced inhibition of BaP-induced carcinogenesis provides a new therapeutic target for the prevention and treatment of environmental hazard induced lung cancer. We found that the expression of several subtypes of the histone H2B was downregulated in BaP-induced carcinogenesis via PARG silencing as determined by label-free proteomics and confirmed by previous cell line- and mouse model-based studies. Analysis using the GEPIA2 online tool indicated that the transcription levels of H2BFS, HIST1H2BD, and HIST1H2BK in lung adenocarcinoma (LUAD) tissues and squamous cell lung carcinoma (LUSC) tissues were higher than those in normal lung tissues, while the transcription levels of HIST1H2BH in LUSC tissues were higher than those in normal lung tissues. The expression levels of HIST1H2BB, HIST1H2BH, and HIST1H2BL were significantly different in different lung cancer (LC) stages. Moreover, the expression of H2BFS, HIST1H2BD, HIST1H2BJ, HIST1H2BK, HIST1H2BL, HIST1H2BO, HIST2H2BE, and HIST2H2BF was positively correlated with that of PARG in LC tissues. Analysis of the Kaplan-Meier plotter database indicated that high H2B levels predicted low survival in all LC patients suggesting that H2B could be a new biomarker for determining the prognosis of the LC, and that its expression can be inhibited by PARG silencing in BaP-induced carcinogenesis.
中文翻译：
聚（ADP-核糖）糖酵解酶沉默介导的 H2B 表达抑制苯并（a）芘诱导的致癌作用
聚（ADP-核糖）糖基水解酶（PARG）是真核生物中水解聚（ADP-核糖）的主要酶，其沉默可以抑制苯并（a）芘（BaP）诱导的致癌作用。深入了解PARG沉默抑制BaP诱发的癌变机制，为环境危害诱发肺癌的防治提供了新的治疗靶点。我们发现组蛋白 H2B 的几种亚型的表达在 BaP 诱导的致癌作用中通过无标记蛋白质组学确定的 PARG 沉默下调，并由先前的细胞系和小鼠模型研究证实。使用 GEPIA2 在线工具分析表明 H2BFS、HIST1H2BD、肺腺癌（LUAD）组织和鳞状细胞肺癌（LUSC）组织中的 HIST1H2BK 和 HIST1H2BK 高于正常肺组织，而 LUSC 组织中 HIST1H2BH 的转录水平高于正常肺组织。HIST1H2BB、HIST1H2BH和HIST1H2BL的表达水平在不同肺癌（LC）分期有显着差异。此外，H2BFS、HIST1H2BD、HIST1H2BJ、HIST1H2BK、HIST1H2BL、HIST1H2BO、HIST2H2BE和HIST2H2BF的表达与LC组织中PARG的表达呈正相关。Kaplan-Meier 绘图仪数据库的分析表明，高 H2B 水平预测所有 LC 患者的低存活率，这表明 H2B 可能是确定 LC 预后的新生物标志物，并且其表达可以通过 BaP 诱导的 PARG 沉默来抑制致癌作用。
更新日期：2020-10-12
中文翻译：
聚（ADP-核糖）糖酵解酶沉默介导的 H2B 表达抑制苯并（a）芘诱导的致癌作用
聚（ADP-核糖）糖基水解酶（PARG）是真核生物中水解聚（ADP-核糖）的主要酶，其沉默可以抑制苯并（a）芘（BaP）诱导的致癌作用。深入了解PARG沉默抑制BaP诱发的癌变机制，为环境危害诱发肺癌的防治提供了新的治疗靶点。我们发现组蛋白 H2B 的几种亚型的表达在 BaP 诱导的致癌作用中通过无标记蛋白质组学确定的 PARG 沉默下调，并由先前的细胞系和小鼠模型研究证实。使用 GEPIA2 在线工具分析表明 H2BFS、HIST1H2BD、肺腺癌（LUAD）组织和鳞状细胞肺癌（LUSC）组织中的 HIST1H2BK 和 HIST1H2BK 高于正常肺组织，而 LUSC 组织中 HIST1H2BH 的转录水平高于正常肺组织。HIST1H2BB、HIST1H2BH和HIST1H2BL的表达水平在不同肺癌（LC）分期有显着差异。此外，H2BFS、HIST1H2BD、HIST1H2BJ、HIST1H2BK、HIST1H2BL、HIST1H2BO、HIST2H2BE和HIST2H2BF的表达与LC组织中PARG的表达呈正相关。Kaplan-Meier 绘图仪数据库的分析表明，高 H2B 水平预测所有 LC 患者的低存活率，这表明 H2B 可能是确定 LC 预后的新生物标志物，并且其表达可以通过 BaP 诱导的 PARG 沉默来抑制致癌作用。
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