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SETDB1 promotes gastric carcinogenesis and metastasis via upregulation of CCND1 and MMP9 expression
Author(s) -
Shang Wenjing,
Wang Yue,
Liang Xiuming,
Li Tongyu,
Shao Wei,
Liu Fen,
Cui Xiujie,
Wang Yuanyuan,
Lv Lin,
Chai Li,
Qu Lingxin,
Zheng Lixin,
Jia Jihui
Publication year - 2021
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.5568
Subject(s) - downregulation and upregulation , cyclin d1 , cancer research , carcinogenesis , mmp9 , biology , transcription factor , metastasis , microbiology and biotechnology , chemistry , cancer , cell cycle , gene , genetics
SETDB1 is a histone lysine methyltransferase that has critical roles in cancers. However, its potential role in gastric cancer (GC) remains obscure. Here, we mainly investigate the clinical significance and the possible role of SETDB1 in GC. We find that SETDB1 expression is upregulated in GC tissues and its high‐level expression was a predictor of poor prognosis in patients. Overexpression of SETDB1 promoted cell proliferation and metastasis, while SETDB1 suppression had an opposite effect both in vitro and in vivo . Mechanistically, SETDB1 was shown to interact with ERG to promote the transcription of cyclin D1 ( CCND1 ) and matrix metalloproteinase 9 ( MMP9 ) through binding to their promoter regions. In addition, the expression of SETDB1 was also enhanced by the transcription factor TCF4 at the transcriptional level in GC. Furthermore, SETDB1 expression was found to be induced by Helicobacter pylori ( H. pylori ) infection in a TCF4‐dependent manner. Taken together, our results indicate that SETDB1 is aberrantly overexpressed in GC and plays key roles in gastric carcinogenesis and metastasis via upregulation of CCND1 and MMP9. Our work also suggests that SETDB1 could be a potential oncogenic factor and a therapeutic target for GC. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.