Histone deacetylase 3 inhibits new tumor suppressor gene DTWD1 in gastric cancer

被引：0
|
作者：
Ma, Yanning [1 ]
Yue, Yongfang [1 ]
Pan, Min [1 ]
Sun, Jie [1 ]
Chu, Jue [1 ]
Lin, Xiaoying [1 ]
Xu, Wenxia [1 ]
Feng, Lifeng [1 ]
Chen, Yan [2 ]
Chen, Dingwei [1 ]
Shin, Vivian Y. [3 ]
Wang, Xian [1 ]
Jin, Hongchuan [1 ]
机构：
[1] Zhejiang Univ, Sir Runrun Shaw Hosp, Key Lab Biotherapy Zhejiang Prov, Lab Canc Biol,Dept Med Oncol, Hangzhou, Zhejiang, Peoples R China
[2] Zhejiang Univ, Hosp 2, Dept Gastroenterol, Hangzhou, Zhejiang, Peoples R China
[3] Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China
来源：
AMERICAN JOURNAL OF CANCER RESEARCH | 2015年 / 5卷 / 02期
基金：
中国国家自然科学基金;
关键词：
HDAC; DTWD1; p53; gastric cancer; tumor suppressor gene; PROSTATE-CANCER; HDAC INHIBITION; P53; ACTIVATION; EXPRESSION; CELLS; CYTOTOXICITY; APOPTOSIS;
D O I：
暂无
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Cancer epigenetics plays an important role in the pathogenesis of many cancers including gastric cancer. Histone deacetylases (HDACs) emerge as exciting therapeutic targets for cancer treatment and prevention. In this study, we identified DTWD1 as one of the 122 genes upregulated after treatment of trichostatin A (TSA) in two gastric cancer cell lines. Moreover, DTWD1 was downregulated in gastric cancer cell lines and primary gastric carcinoma tissues. It was further identified as the new target of p53. Then we revealed that HDAC3 downregulated DTWD1 by disrupting the interaction of p53 with DTWD1 promoter. Furthermore, DTWD1 functioned as a tumor suppressor by downregulating cyclin B1 expression to inhibit proliferation. In summary, as the new p53 target gene, DTWD1 was downregulated in gastric cancer by HDAC3 and acted as a novel tumor suppressor gene. Specific inhibitors of HDAC3 might be a new approach for gastric cancer treatment by activating DTWD1 expression.
引用
收藏
页码：663 / 673
页数：11
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