HOXD9 promotes the growth, invasion and metastasis of gastric cancer cells by transcriptional activation of RUFY3

被引：50

作者：

Zhu, Huiqiong ^{[1
]}

Dai, Weiyu ^{[1
]}

Li, Jiaying ^{[1
]}

Xiang, Li ^{[2
]}

Wu, Xiaosheng ^{[1
]}

Tang, Weimei ^{[1
]}

Chen, Yaying ^{[3
]}

Yang, Qiong ^{[1
]}

Liu, Mengwei ^{[1
]}

Xiao, Yizhi ^{[1
]}

Zhang, Wenjing ^{[4
]}

Lin, Jianjiao ^{[1
,2
]}

Wang, Jing ^{[1
]}

Liu, Guangnan ^{[1
]}

Sun, Yong ^{[1
]}

Jiang, Ping ^{[1
]}

Li, Guoxin ^{[5
]}

Li, Aimin ^{[1
]}

Liu, Side ^{[1
,2
,6
]}

Chen, Ye ^{[1
,6
]}

Wang, Jide ^{[1
,2
,6
]}

机构：

[1] Southern Med Univ, Nanfang Hosp, Dept Gastroenterol, Guangdong Prov Key Lab Gastroenterol, Guangzhou 510515, Guangdong, Peoples R China

[2] Longgang Dist Peoples Hosp, Dept Gastroenterol, Shenzhen 518172, Peoples R China

[3] Guangzhou Med Univ, Affiliated Hosp 3, Dept Gastroenterol, Guangzhou 510515, Guangdong, Peoples R China

[4] Kunming Univ Sci & Technol, Peoples Hosp Yunnan Prov 1, Med Sch, Dept Med Oncol, Kunming 650032, Yunnan, Peoples R China

[5] Southern Med Univ, Nanfang Hosp, Dept Gen Surg, Guangzhou 510515, Guangdong, Peoples R China

[6] Southern Med Univ, Nanfang Hosp, Dept Digest Med, Guangzhou 510515, Guangdong, Peoples R China

来源：

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH | 2019年 / 38卷 / 01期

关键词：

HOXD9; RUFY3; Gastric cancer; Proliferation; Metastasis; EPITHELIAL-MESENCHYMAL TRANSITION; PROTEIN-KINASE; ADHESION MOLECULE; COLORECTAL-CANCER; HOMEOBOX GENES; SELF-RENEWAL; EXPRESSION; MAPKS; PROLIFERATION; APOPTOSIS;

D O I：

10.1186/s13046-019-1399-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background The 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. Methods In 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. Results HOXD9 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. Conclusions The evidence presented here suggests that the HOXD9-RUFY3 axis promotes the development and progression of human GC.

引用

页数：15

共 42 条

[1] Overexpression of HOXA4 and HOXA9 genes promotes self-renewal and contributes to colon cancer stem cell overpopulation [J].