HOXC10 up-regulation promotes gastric cancer cell proliferation and metastasis through MAPK pathway  

作　　者：Chen Guo Jianing Hou Sheng Ao Xingming Deng Guoqing Lyu 

机构地区：[1]Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Peking University,Beijing 100191,China [2]Department of Gastrointestinal Surgery,Peking University Shenzhen Hospital,Shertzhen 518036,China

出　　处：《Chinese Journal of Cancer Research》2017年第6期572-580,共9页中国癌症研究（英文版）

基　　金：supported by the grants from‘San Ming’Project of Shenzhen city,China;Municipal Health planning Commission Fund of Shenzhen city,China(No.201601004 and No.201704260051)

摘　　要：Objective： As an important regulator of embryonic morphogenesis, homeodomain-containing gene 10 （HOXC10） has been found to promote progression of human cancers and its expression indicates poor survival outcome. However, very few studies are available on the role of HOXC10 in gastric carcinoma. Therefore, the aim of this study was to determine the role of HOXC10 in gastric cancer and the potential mechanism underlying its function for cancer biology. Methods： A primary gastric cancer mouse model was obtained via intra-gastric wall injection of gastric cancer cells and was used to evaluate the function of HOXC10 during gastric cancer progression in vivo. Immunohistochemistry was performed to visualize and measure HOXC10 protein expression in gastric cancer tissue. Cells were transfected with plasmids to increase the expression of HOXCIO, and siRNA transfection was performed to suppress HOXC10 expression. Reverse transcription polymerase chain reaction （RT-PCR） and western blotting were utilized to measure mRNA and protein expression, respectively. Proliferation, migration, and invasion were investigated using 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay, wound healing assay, and matrigel invasion assay in vitro, respectively. Results： HOXC10 expression was significantly increased in gastric cancer tissues compared to matched normal tissues. HOXC10 up-regulation significantly increased tumor volumes in nude mice. Plasmid transfection significantly increased HOXC10 protein and mRNA expressions and effectively promoted cell proliferation. Moreover, HOXC10 up-regulation significantly promoted migration and invasion of gastric cancer cells. Mechanistic investigation showed that HOXC10 up-regulation significantly increased mRNA and protein expression of mitogen-activated protein kinase （MAPK） signaling related genes, including c-myc, c-jun and p53, while also modulating the phosphorylation of c-Jun N-terminal kinase （JNK）, extracellular signal-regulated kinase �Objective： As an important regulator of embryonic morphogenesis, homeodomain-containing gene 10 （HOXC10） has been found to promote progression of human cancers and its expression indicates poor survival outcome. However, very few studies are available on the role of HOXC10 in gastric carcinoma. Therefore, the aim of this study was to determine the role of HOXC10 in gastric cancer and the potential mechanism underlying its function for cancer biology. Methods： A primary gastric cancer mouse model was obtained via intra-gastric wall injection of gastric cancer cells and was used to evaluate the function of HOXC10 during gastric cancer progression in vivo. Immunohistochemistry was performed to visualize and measure HOXC10 protein expression in gastric cancer tissue. Cells were transfected with plasmids to increase the expression of HOXCIO, and siRNA transfection was performed to suppress HOXC10 expression. Reverse transcription polymerase chain reaction （RT-PCR） and western blotting were utilized to measure mRNA and protein expression, respectively. Proliferation, migration, and invasion were investigated using 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay, wound healing assay, and matrigel invasion assay in vitro, respectively. Results： HOXC10 expression was significantly increased in gastric cancer tissues compared to matched normal tissues. HOXC10 up-regulation significantly increased tumor volumes in nude mice. Plasmid transfection significantly increased HOXC10 protein and mRNA expressions and effectively promoted cell proliferation. Moreover, HOXC10 up-regulation significantly promoted migration and invasion of gastric cancer cells. Mechanistic investigation showed that HOXC10 up-regulation significantly increased mRNA and protein expression of mitogen-activated protein kinase （MAPK） signaling related genes, including c-myc, c-jun and p53, while also modulating the phosphorylation of c-Jun N-terminal kinase （JNK）, extracellular signal-regulated kinase �

关 键 词：HOXCIO PROLIFERATION METASTASIS gastric cancer 

分 类 号：R735.2[医药卫生—肿瘤]