Ling Zhi-Qiang, Ge Ming-Hua, Lu Xiao-Xiao, Han Jin, Wu Yi-Chen, Liu Xiang, Zhu Xin, Hong Lian-Lian
Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, China.
Department of Tumor Surgery, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, China.
Oncotarget. 2015 Apr 10;6(10):8210-25. doi: 10.18632/oncotarget.3601.
N-myc downstream regulated gene 2 (Ndrg2) is a candidate suppressor of cancer metastasis. We found that Ndrg2 promoter was frequently hypermethylated in gastric cancer cell lines and in 292 gastric tumor tissues. This resulted in down-regulation of Ndrg2 mRNA and protein. Ndrg2 promoter methylation was associated with H. pylori infection and worse prognosis of gastric cancer patients, which is an independent prognostic factor for the disease-free survival (DFS). We found that H. pylori silenced Ndrg2 by activating the NF-κB pathway and up-regulating DNMT3b, promoting gastric cancer progression. These findings uncover a previously unrecognized role for H. pylori infection in gastric cancer.
N-myc下游调控基因2（Ndrg2）是一种癌症转移的候选抑制因子。我们发现，Ndrg2启动子在胃癌细胞系和292例胃肿瘤组织中频繁发生高甲基化。这导致Ndrg2 mRNA和蛋白表达下调。Ndrg2启动子甲基化与幽门螺杆菌感染及胃癌患者较差的预后相关，是无病生存期（DFS）的独立预后因素。我们发现，幽门螺杆菌通过激活NF-κB通路和上调DNMT3b使Ndrg2沉默，从而促进胃癌进展。这些发现揭示了幽门螺杆菌感染在胃癌中以前未被认识到的作用。
