Poly(ADP-ribose) glycohydrolase silencing-mediated H2B expression inhibits benzo(a)pyrene-induced carcinogenesis.

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.