组蛋白去乙酰化酶3抑制胃癌中的新肿瘤抑制基因DTWD1。
Histone deacetylase 3 inhibits new tumor suppressor gene DTWD1 in gastric cancer.
作者信息
Ma Yanning, Yue Yongfang, Pan Min, Sun Jie, Chu Jue, Lin Xiaoying, Xu Wenxia, Feng Lifeng, Chen Yan, Chen Dingwei, Shin Vivian Y, Wang Xian, Jin Hongchuan
机构信息
Laboratory of Cancer Biology, Department of Medical Oncology, Key laboratory of Biotherapy in Zhejiang Province, Sir Runrun Shaw Hospital Zhejiang University, China.
Departrment of Gastroenterology, The 2nd Hospital of Zhejiang University China.
出版信息
Am J Cancer Res. 2015 Jan 15;5(2):663-73. eCollection 2015.
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.
癌症表观遗传学在包括胃癌在内的多种癌症发病机制中发挥着重要作用。组蛋白去乙酰化酶（HDACs）成为癌症治疗和预防中令人兴奋的治疗靶点。在本研究中，我们确定DTWD1是两种胃癌细胞系经曲古抑菌素A（TSA）处理后上调的122个基因之一。此外，DTWD1在胃癌细胞系和原发性胃癌组织中表达下调。它进一步被确定为p53的新靶点。然后我们发现HDAC3通过破坏p53与DTWD1启动子的相互作用而下调DTWD1。此外，DTWD1通过下调细胞周期蛋白B1表达来抑制增殖，从而发挥肿瘤抑制作用。总之，作为新的p53靶基因，DTWD1在胃癌中被HDAC3下调，并作为一种新的肿瘤抑制基因发挥作用。HDAC3的特异性抑制剂可能是通过激活DTWD1表达来治疗胃癌的一种新方法。
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