期刊
CARCINOGENESIS
卷 41, 期 5, 页码 678-688出版社
OXFORD UNIV PRESS
DOI: 10.1093/carcin/bgz131
关键词
-
类别
资金
- National Natural Science Foundation of China [81672992, 81872470]
- Guangdong Natural Science Funds for Distinguished Young Scholar [2015A030306015]
- Excellent Young Teachers Program of Higher Education of Guangdong Province [YQ2015036]
- Guangdong Program for Support of Top-notch Young Professionals [2015TQ01R279]
- Natural Science Foundation of Guangdong [2018030310297]
Upregulation of histone methyltransferase SET domain bifurcated 1 (SETDB1) is associated with poor prognosis in cancer patients. However, the mechanism of oncogenicity of SETDB1 in cancer is hitherto unknown. Here, we show that SETDB1 is upregulated in human colorectal cancer (CRC) where its level correlates with poor clinical outcome. Ectopic SETDB1 promotes CRC cell proliferation, whereas SETDB1 attenuation inhibits this process. Flow cytometry reveals that SETDB1 promotes proliferation by driving the CRC cell cycle from G(0)/G(1) phase to S phase. Mechanistically, SETDB1 binds directly to the STAT1 promoter region resulting in increased STAT1 expression. Functional characterization reveals that STAT1-CCND1/CDK6 axis is a downstream effector of SETDB1-mediated CRC cell proliferation. Furthermore, SETDB1 upregulation is sufficient to accelerate in vivo proliferation in xenograft animal model. Taken together, our results provide insight into the upregulation of SETDB1 within CRC and can lead to novel treatment strategies targeting this cell proliferation-promoting gene.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据