HOXD9 promotes the growth, invasion and metastasis of gastric cancer cells by transcriptional activation of RUFY3
HOXD9 promotes the growth, invasion and metastasis of gastric cancer cells by transcriptional activation of RUFY3
复制标题
HOXD9通过转录激活RUFY3促进胃癌细胞的生长、侵袭和转移
DOI：
10.1186/s13046-019-1399-1
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发表时间：
2019
影响因子：
11.3
通讯作者：
Wang Jide
中科院分区：
文献类型：
--
作者：
Zhu Huiqiong;Dai Weiyu;Li Jiaying;Xiang Li;Wu Xiaosheng;Tang Weimei;Chen Yaying;Yang Qiong;Liu Mengwei;Xiao Yizhi;Zhang Wenjing;Lin Jianjiao;Wang Jing;Liu Guangnan;Sun Yong;Jiang Ping;Li Guoxin;Li Aimin;Liu Side;Chen Ye;Wang Jide
研究背景转录因子HOXD 9是HOX家族成员之一，在肿瘤发生发展中起重要作用。然而，HOXD 9在胃癌（GC）的生长和转移中的作用仍有待阐明。MethodsIn vitro functional role of HOXD 9 and RURY 3 in GC cells was determined using TMA-based immunohistochemistry，western blot，EdU incorporation，gelatin zymography，luciferase，chromatin Immunoprecipitation（ChIP）and cell invasion assays.结果HOXD 9在胃癌细胞和胃癌组织中均过表达，胃癌患者HOXD 9的高表达与胃癌患者的生存率相关。HOXD 9的表达在功能上显著促进胃癌细胞的增殖、侵袭和迁移。在机械上，HOXD 9直接与RUFY3启动子结合以增加RUFY3的转录活性。抑制RUFY3可以在体外和体内减弱HOXD 9过表达GC细胞的增殖、迁移和侵袭力。此外，HOXD 9和RUFY3在胃癌细胞中高表达，而在正常胃组织中不表达，二者的表达呈正相关. ConclusionsThe证据提示HOXD 9-RUFY3轴促进人胃癌的发生和发展.
BackgroundThe transcription factor HOXD9 is one of the members of the HOX family, which plays an important role in neoplastic processes. However, the role of HOXD9 in the growth and metastasis of gastric cancer (GC) remains to be elucidated.MethodsIn vitro functional role of HOXD9 and RURY3 in GC cells was determined using the TMA-based immunohistochemistry, western blot, EdU incorporation, gelatin zymography, luciferase, chromatin Immunoprecipitation (ChIP) and cell invasion assays. In vivo tumor growth and metastasis were conducted in nude mice.ResultsHOXD9 is overexpressed in GC cells and tissues.The high expression of HOXD9 was correlated with poor survival in GC patients. Functionally, HOXD9 expression significantly promoted the proliferation, invasion and migration of GC cells. Mechanically, HOXD9 directly associated with the RUFY3 promoter to increase the transcriptional activity of RUFY3. Inhibition of RUFY3 attenuated the proliferation, migration and invasiveness of HOXD9-overexpressing GC cells in vitro and in vivo. Moreover, both HOXD9 and RUFY3 were highly expressed in cancer cells but not in normal gastric tissues, with their expressions being positively correlated.ConclusionsThe evidence presented here suggests that the HOXD9-RUFY3 axis promotes the development and progression of human GC.