Objectives: Gastric cancer ranks the fourth most common cancer and the third leading cause of cancer mortality in the world. ROS proto-oncogene 1 (ROS1 ) is an oncogene and ROS1  rearrangement has been reported in many cancers. Our study aimed to investigate the potential function and the precise mechanisms of ROS1  in gastric cancer.
Methods: In our study, the analysis of ROS1  expression and clinical pathologic factors of gastric cancer in gastric cancer using TCGA database demonstrated that ROS1  expression was elevated in gastric cancer and related to T, N, M and TNM staging. High expression of ROS1  predicted poor survival in patients with gastric cancer. Then, we measured ROS1  expression in four human gastric cancer cell lines and knocked down ROS1  expression in BGC-823 and SGC-7901 cells by specific shRNA transfection via Lipofectamine 2000. The effect of ROS1  knockdown on cell proliferation, cell cycle distribution, cell apoptosis and metastasis in vitro was evaluated by MTT, colony formation, flow cytometric analysis, wound healing and Transwell invasion assays. The levels of apoptosis-related proteins, EMT markers and the PI3K/Akt signaling pathway members were measured by Western blotting.
Results: We demonstrated that shROS1  transfection markedly downregulated ROS1 expression in BGC-823 and SGC-7901 cells. Knockdown of ROS1  inhibited cell survival, clonogenic growth, migration, invasion and epithelial–mesenchymal transition (EMT), as well as induced cell cycle arrest and apoptosis in gastric cancer cells. Furthermore, ROS1  knockdown inhibited the phosphorylation of PI3K and Akt.
Conclusion: Collectively, our data suggest that ROS1  may serve as a promising therapeutic target in gastric cancer treatment.
Keywords: gastric cancer, ROS1 , shRNA, proliferation, apoptosis, metastasis, EMT