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首页> 外文期刊>EBioMedicine >CHAF1A interacts with TCF4 to promote gastric carcinogenesis via upregulation of c-MYC and CCND1 expression
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CHAF1A interacts with TCF4 to promote gastric carcinogenesis via upregulation of c-MYC and CCND1 expression

机译：CHAF1A与TCF4相互作用以通过上调c-MYC和CCND1表达来促进胃癌发生

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Background Histones chaperones have been found to play critical roles in tumor development and progression. However, the role of histone chaperone CHAF1A in gastric carcinogenesis and its underlying mechanisms remain elusive. Methods CHAF1A expression in gastric cancer (GC) was analyzed in GEO datasets and clinical specimens. CHAF1A knockdown and overexpression were used to explore its functions in gastric cancer cells. The regulation and potential molecular mechanism of CHAF1A expression in gastric cancer cells were studied by using cell and molecular biological methods. Findings CHAF1A was upregulated in GC tissues and its high expression predicted poor prognosis in GC patients. Overexpression of CHAF1A promoted gastric cancer cell proliferation both in vitro and in vivo, whereas CHAF1A suppression exhibited the opposite effects. Mechanistically, CHAF1A acted as a co-activator in the Wnt pathway. CHAF1A directly interacted with TCF4 to enhance the expression of c-MYC and CCND1 through binding to their promoter regions. In addition, the overexpression of CHAF1A was modulated by specificity protein 1 (Sp1) in GC. Sp1 transcriptionally enhanced the expression of CHAF1A in GC. Furthermore, CHAF1A expression induced by Helicobacter pylori was Sp1 dependent. Interpretation CHAF1A is a potential oncogene in GC, and may serve as a novel therapeutic target for GC treatment.
机译：背景技术已发现组蛋白伴侣在肿瘤发展和进展中起关键作用。但是，组蛋白伴侣CHAF1A在胃癌发生过程中的作用及其潜在机制仍不清楚。方法用GEO数据集和临床标本分析CHAF1A在胃癌（GC）中的表达。 CHAF1A敲低和过度表达被用来探索其在胃癌细胞中的功能。利用细胞和分子生物学方法研究了CHAF1A在胃癌细胞中的表达调控及其潜在的分子机制。结果CHAF1A在GC组织中上调，其高表达预示了GC患者的预后不良。 CHAF1A的过表达在体外和体内均促进胃癌细胞的增殖，而CHAF1A的抑制则表现出相反的作用。从机理上讲，CHAF1A在Wnt途径中充当共激活因子。 CHAF1A直接与TCF4相互作用，通过与启动子区域结合来增强c-MYC和CCND1的表达。此外，CHAF1A的过表达受GC中的特异性蛋白1（Sp1）调控。 Sp1转录增强了CHAF1A在GC中的表达。此外，幽门螺杆菌诱导的CHAF1A表达是Sp1依赖性的。解释CHAF1A是GC中潜在的致癌基因，可作为GC治疗的新治疗靶标。

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