Anti-silencing function 1B promotes the progression of pancreatic cancer by activating c-Myc

The present study aimed to explore the role of histone chaperone anti-silencing function 1B (ASF1B) in pancreatic cancer and the underlying mechanism. The biological function of ASF1B was investigated in pancreatic cancer cell lines (PANC-1 and SW1990) and a mouse xenograft model. Chromatin immunoprecipitation was used to detect the effect of ASF1B on the transcriptional activity of c-Myc. ASF1B was highly expressed in pancreatic adenocarcinoma (PAAD) samples from The Cancer Genome Atlas. ASF1B expression was positively associated with poor survival rates in patients with PAAD. Silencing of ASF1B in PANC-1 and SW1990 cells inhibited cell proliferation, migration and invasion, and induced apoptosis. Mechanistically, ASF1B increased H3K56 acetylation (H3K56ac) in a CREB-binding protein (CBP)-dependent manner. ASF1B promoted H3K56ac at the c-Myc promoter and increased c-Myc expression. In PANC-1 and SW1990 cells, the CBP inhibitor curcumin and the c-Myc inhibitor 10058-F4 reversed the promoting effects of ASF1B on cell proliferation, migration and invasion. In the mouse xenograft model, ASF1B silencing inhibited tumor growth, and was associated with low H3K56ac and c-Myc expression. ASF1B promoted pancreatic cancer progression by activating c-Myc via CBP-mediated H3K56ac.