Enhanced cell survival of gastric cancer cells by a novel gene URG4

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.