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

被引:5
作者
Zhang, Min [1 ]
Zhang, Luyang [1 ]
Zhou, Minghe [1 ]
Wang, Enze [1 ]
Meng, Bo [1 ]
Li, Qingjun [1 ]
Wang, Xiaoqian [1 ]
Wang, Yunjian [1 ]
Li, Qiong [2 ]
机构
[1] Zhengzhou Univ, Affiliated Canc Hosp, Dept Hepatobiliary & Pancreat Surg, 127 Dongming Rd, Zhengzhou 450008, Henan, Peoples R China
[2] Xinxiang Med Coll, Key Lab Med Tissue Regenerat Henan Prov, 601 Jinsui Ave, Xinxiang 453003, Henan, Peoples R China
基金
中国国家自然科学基金;
关键词
pancreatic cancer; ASF1B; c-Myc; CBP; HISTONE CHAPERONE ASF1; GENE-EXPRESSION; LYSINE; 56; ACETYLATION; TARGET; H3; PROLIFERATION; CHROMATIN; SIRT6;
D O I
10.3892/ijo.2022.5456
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页数:13
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