Poly(Adp-Ribose) Glycohydrolase Silencing-Mediatedh2bexpression 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 ofPARGsilenced 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 viaPARGsilencing 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 ofH2BFS,HIST1H2BD, andHIST1H2BKin lung adenocarcinoma (LUAD) tissues and squamous cell lung carcinoma (LUSC) tissues were higher than those in normal lung tissues, while the transcription levels ofHIST1H2BHin LUSC tissues were higher than those in normal lung tissues. The expression levels ofHIST1H2BB,HIST1H2BH, andHIST1H2BLwere significantly different in different lung cancer (LC) stages. Moreover, the expression ofH2BFS,HIST1H2BD,HIST1H2BJ,HIST1H2BK,HIST1H2BL,HIST1H2BO,HIST2H2BE, andHIST2H2BFwas positively correlated with that ofPARGin 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 byPARGsilencing in BaP-induced carcinogenesis.