Histone Deacetylase 3 Inhibits New Tumor Suppressor Gene DTWD1 in Gastric Cancer

Overview

Journal Am J Cancer Res

Specialty Oncology

Date 2015 May 15

PMID 25973305

Citations 21

Authors

Yanning Ma

Yongfang Yue

Min Pan

Jie Sun

Jue Chu

Xiaoying Lin

Wenxia Xu

Lifeng Feng

Yan Chen

Dingwei Chen

Vivian Y Shin

Xian Wang

Hongchuan Jin

Affiliations

Soon will be listed here.

Abstract

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.

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