标题:CHAF1A interacts with TCF4 to promote gastric carcinogenesis via upregulation of c-MYC and CCND1 expression
作者:Zheng, Lixin; Liang, Xiuming; Li, Shuyan; Li, Tongyu; Shang, Wenjing; Jia, Xiaxia; Shao, Wei; Sun, Pengpeng; Chen, Chunyan; Jia, Jih 更多
作者机构:[Zheng, Lixin; Liang, Xiuming; Li, Shuyan; Li, Tongyu; Shang, Wenjing; Jia, Xiaxia; Shao, Wei; Sun, Pengpeng; Jia, Jihui] Shandong Univ, Sch Basic Med 更多
通讯作者:Jia, JH
通讯作者地址:[Jia, JH]Shandong Univ, Sch Basic Med Sci, Chinese Minist Educ, Dept Microbiol,Key Lab Expt Teratol, Jinan 250012, Shandong, Peoples R China.
来源:EBIOMEDICINE
出版年:2018
卷:38
页码:69-78
DOI:10.1016/j.ebiom.2018.11.009
关键词:Histone chaperone; CHAF1A; Gastric cancer; Carcinogenesis
摘要: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. (c) 2018 The Authors. Published by Elsevier B.V.
收录类别:SCOPUS;SCIE
WOS核心被引频次:1
Scopus被引频次:1
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85056540400&doi=10.1016%2fj.ebiom.2018.11.009&partnerID=40&md5=dd22bc75686f248e8f61ad44da28bfaa
TOP