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Transcriptional repression and apoptosis influence the effect of APOBEC3A/3B functional polymorphisms on biliary tract cancer risk

ABSTRACT: APOBEC3s-related somatic mutations are the predominant burden in biliary tract cancers (BTCs). Here, we reveal the effects and mechanisms of APOBEC3A/3B functional polymorphisms on cholangiocarcinoma and gallbladder cancer (GBC). rs2267401-G at the APOBEC3B promoter decreases cholangiocarcinoma risk but increased GBC risk. rs2267401-G confers a decreased APOBEC3B promoter activity in cholangiocarcinoma cells but an increased activity in GBC cells. rs12157810-C at the APOBEC3A promoter decreases the risk of BTCs. rs12157810-C up-regulated the promoter activity in both cells. APOBEC3A overexpression attenuates cancer evolution via causing apoptosis, in contrast to APOBEC3B. Inflammatory factors promote cancer evolution via interacting with transcriptional repressors regulating the APOBEC3A/3B promoters. ATAC-seq was used to identify the difference between transcriptional networks of cholangiocarcinoma and GBC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE166372 | GEO | 2022/01/07

REPOSITORIES: GEO

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