Enhanced cell survival of gastric cancer cells by a novel gene URG4
Enhanced cell survival of gastric cancer cells by a novel gene URG4
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新基因URG4增强胃癌细胞的存活率
DOI：
10.1593/neo.06592
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发表时间：
2006-12-01
期刊：
影响因子：
4.8
通讯作者：
Fan, Daiming
中科院分区：
文献类型：
--
作者：
Song, Jiugang;Xie, Huahong;Fan, Daiming
上调基因4(URG4)是位于7号染色体(7p13)上的一个新基因，与肝癌的发生有关。然而，URG4在胃癌发生中的作用仍不清楚。在本研究中，免疫组织化学发现URG4在人胃癌组织中表达上调，而在匹配的癌旁非肿瘤组织中表达上调。URG4高表达的胃癌组织增殖细胞核抗原指数高于低表达的胃癌组织。在URG4诱导下，GES-1细胞的生长速度加快，GES-1细胞是具有URG4基础表达的永生化人胃粘膜上皮细胞。在内源性URG4高表达的SGC7901和MKN28细胞中，通过URG4小干扰RNA(SiRNA)下调URG4表达可抑制这两种细胞的增殖。URG4-siRNA还能抑制SGC7901和MKN28细胞在软琼脂中的增殖和裸鼠体内成瘤。URG4在GES细胞中的过表达上调了细胞周期蛋白D1的表达，而在SGC7901和MKN28细胞中的表达下调了细胞周期蛋白D1的表达。提示URG4可能通过调控细胞周期蛋白D1的表达在人胃癌的发生发展过程中发挥重要作用，有可能成为胃癌治疗的新靶点。
Upregulated gene 4 (URG4), a novel gene located on 7 chromosome (7p13), was found to contribute to hepatocarcinogenesis. However, the role of URG4 in the gastric carcinogenesis still remains unclear. In the present study, URG4 was found by immunohistochemistry to be upregulated in human gastric cancer tissues compared with matched adjacent nonneoplastic tissues. The proliferating cell nuclear antigen index is higher in gastric cancer tissues with high URG4 expression than in those with low URG4 expression. The growth of GES-1 cells, which are immortalized human gastric epithelial mucosa cells with baseline URG4 expression, was accelerated by URG4 induction. Downregulation of URG4 through URG4 small interfering RNA (siRNA) in SGC7901 and MKN28 cells, which had high endogenous URG4 expression, suppressed cell proliferation in both of these cells. URG4-siRNA also inhibited the proliferation of SGC7901 and MKN28 cells in soft agar and tumor formation in nude mice. Overexpression of URG4 in GES cells upregulated cyclin D1, whereas repression of URG4 in SGC7901 and MKN28 cells downregulated cyclin D1. The data suggested that URG4 played an important role in the development of human gastric cancer by regulating the expression of cyclin D1 and might be used as a potential therapeutic target for gastric cancer.