聚(ADP-核糖)糖水解酶在苯并[a]芘诱导肺癌发生过程中的作用及机制OA

OBJECTIVE:To investigate the role and mechanism of poly(ADP-ribose)glycohydrolase(PARG)in benzo[a]pyrene(BaP)-induced lung carcinogenesis,with a focus on its association with DNA replication-related pathways.METHODS:Based on a BaP-induced malignant transformation model of human bronchial epithelial cells,transcriptomic microarray analysis was performed to identify differentially expressed genes(DEGs)under PARG low-expression conditions.Functional and pathway enrichment analyses were conducted using the Metascape platform.The molecular complex detection(MCODE)algorithm was applied to construct protein-protein interaction networks and to identify core regulatory genes associated with PARG.Expression patterns of these core genes in lung cancer tissues were further evaluated using the GEPIA2 database,and their prognostic relevance was evaluated using the Kaplan-Meier Plotter database.RESULTS:Transcriptomic analysis identified a set of DEGs associated with PARG regulation,among which the core genes were significantly enriched in DNA replication-related pathways(P<0.05).Correlation analysis showed that the expression levels of MCM2-7,DNA2,FEN1,PCNA,POLE2 and RFC3 were positively correlated with PARG expression in lung cancer tissues(P<0.01).These core genes were significantly upregulated in lung adenocarcinoma and/or lung squamous cell carcinoma and exhibited stage-dependent expression patterns.Survival analysis further showed that the high expression levels of MCM2,MCM4,and POLD1 were significantly associated with poor overall survival(OS),progression-free survival(PFS),and post-progression survival(PPS)in lung cancer patients(P<0.05).CONCLUSION:Low PARG expression influenced expression characteristics of DNA replication-related genes during BaP-induced lung carcinogenesis.These PARG-related molecules showed aberrant expression patterns and prognostic relevance in lung cancer tissues,suggesting that they may play an important role in BaP-associated lung carcinogenesis.