Malignant transformation of human bronchial epithelial cells induced by benzo [a] pyrene suggests a negative feedback of TP53 to PPP1R13L via binding a possible enhancer element.

Previous studies have shown that PPP1R13L as an inhibitor of apoptosis protease TP53 can lead to abnormal cell proliferation and carcinogenesis, however, the function of PPP1R13L was complicated and the interaction between TP53 and PPP1R13L needs to be further explored. In the present study, a malignant transformation model of human bronchial epithelial cells induced by benzo (a) pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) was established to observe the regulatory patterns between TP53 and PPP1R13L during carcinogenesis. In vitro experiments including CRISPR-Cas9 editing, RNA silence, Co-Immunoprecipitation and Chromatin Immunoprecipitation were applied to discuss their interactive effects. Additionally, TCGA data profile and our clinical samples of lung cancer were also used to analyze their relationship at the transcriptome level. Interestingly, we found that the mRNA and protein level of TP53 and PPP1R13L fluctuated as a wave in BPDE-induced malignant transformation under wild-type TP53 genetic background. Our results have also demonstrated that PPP1R13L acts as an inhibitor of TP53, while TP53 can regulate PPP1R13L via binding a possible enhancer of the first intron of PPP1R13L gene. Likewise, TCGA data and clinical samples have identified that in the case of TP53 mutation, TP53 expression was negatively correlated with PPP1R13L, while in the case of TP53 wild-type, TP53 expression was not correlated with PPP1R13L. It suggested that there existed a negative feedback of wild-type TP53 to PPP1R13L, which reminded a unique implication during chemical carcinogenesis.