标题：GAGE7B promotes tumor metastasis and growth via activating the p38/pMAPKAPK2/pHSP27 pathway in gastric cancer
作者：Shi, Duan-Bo; Ma, Ran-Ran; Zhang, Hui; Hou, Feng; Guo, Xiang-Yu; Gao, Peng
作者机构：[Shi, Duan-Bo; Ma, Ran-Ran; Zhang, Hui; Hou, Feng; Guo, Xiang-Yu; Gao, Peng] Shandong Univ, Sch Med, Dept Pathol, Jinan 250012, Shandong, Peoples R Ch 更多
通讯作者：Gao, P;Gao, P
通讯作者地址：[Gao, P]Shandong Univ, Sch Med, Dept Pathol, Jinan 250012, Shandong, Peoples R China;[Gao, P]Shandong Univ, Qilu Hosp, Dept Pathol, Jinan 250012, Shan 更多
来源：JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
关键词：GAGE7B; Gastric cancer; Metastasis; Growth
摘要：BackgroundGastric cancer is the second most common cause of cancer-related mortality; thus, the mechanisms underlying tumor metastasis and growth in gastric cancer need to be extensively explored.MethodsDifferentially expressed genes were examined in gastric cancer samples with lymph node metastasis (LNM) and without LNM using mRNA microarray and RT-qPCR. The effects of G antigen 7B (GAGE7B) on the metastasis, growth, and angiogenesis of gastric cancer were investigated in vitro and in vivo. GAGE7B protein expression was detected by immunohistochemical (IHC) analysis. Microarray, RT-qPCR, and western blot assays were performed to detect downstream target genes of GAGE7B. Dual-luciferase reporter and western blot assays were used to identify miRNAs that could negatively regulate GAGE7B.ResultsGAGE7B was significantly overexpressed in samples with LNM. High expression levels of GAGE7B were associated with advanced clinical stage and poor patient survival. GAGE7B dramatically enhanced the metastasis, growth, and angiogenesis ability of gastric cancer. GAGE7B was further demonstrated to promote the progression of gastric cancer by activating the p38/pMAPKAPK2/pHSP27 pathway. However, the GAGE7B-induced p38/pMAPKAPK2/pHSP27 pathway was inactivated by miR-30c, as the expression levels of both GAGE7B and p38 were found to be directly suppressed by miR-30c. Intriguingly, GAGE7B was found to be a ceRNA for p38, as it activated the p38/pMAPKAPK2/pHSP27 pathway by competitively binding miR-30c.ConclusionsGAGE7B may serve as a prognostic indicator in gastric cancer. GAGE7B significantly promotes gastric cancer progression by upregulating the p38/pMAPKAPK2/pHSP27 pathway, but it is negatively regulated by miR-30c. GAGE7B and miR-30c may be potential therapeutic targets in gastric cancer.