Sun Lisha, Chen Guanglei, Sun Anqi, Wang Zheng, Huang Haibo, Gao Ziming, Liang Weitian, Liu Caigang, Li Kai
Department of Surgical Oncology, The First Hospital of China Medical University, Shenyang, China.
Department of Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, China.
Front Oncol. 2020 Jan 31;10:31. doi: 10.3389/fonc.2020.00031. eCollection 2020.
Bcl2-associated athanogene (BAG)2 as a co-chaperone has been demonstrated to be involved in tumor growth and metastasis, but its biological function in gastric cancer remains unknown. Here, we reported that BAG2 was highly expressed in gastric cancer cell lines and tissues, indicating poor prognosis. High expression of BAG2 was significantly associated with T stage and differentiation level of gastric cancer ( < 0.001). Functional experiments revealed that knockdown in gastric cancer cells inhibited the proliferation, invasion and migration of cells through AKT/mTOR and extracellular regulated kinase (ERK) pathways. Proteomic analysis identified that BAG2 may be involved in the regulation of mitogen-activated protein kinase (MAPK) pathway. In addition, immunoprecipitation showed that BAG2 could bind to ERK1/2. Luciferase reporter assay and Western blot verified that was down-regulated by miR186. Taken together, our findings may reveal the basic function of BAG2 and uncover a potential therapeutic target for gastric cancer.
作为一种共伴侣蛋白，Bcl2相关抗凋亡基因（BAG）2已被证明参与肿瘤生长和转移，但其在胃癌中的生物学功能尚不清楚。在此，我们报道BAG2在胃癌细胞系和组织中高表达，提示预后不良。BAG2的高表达与胃癌的T分期和分化程度显著相关（<0.001）。功能实验表明，敲低胃癌细胞中的BAG2可通过AKT/mTOR和细胞外调节激酶（ERK）途径抑制细胞的增殖、侵袭和迁移。蛋白质组学分析确定BAG2可能参与丝裂原活化蛋白激酶（MAPK）途径的调控。此外，免疫沉淀显示BAG2可与ERK1/2结合。荧光素酶报告基因检测和蛋白质免疫印迹证实miR186可下调BAG2。综上所述，我们的研究结果可能揭示了BAG2的基本功能，并为胃癌发现了一个潜在的治疗靶点。
