MAGOH/MAGOHB Inhibits the Tumorigenesis of Gastric Cancer via Inactivation of b-RAF/MEK/ERK Signaling

BACKGROUND: Gastric cancer is one of the most malignant tumors all over the world. It has been reported that proteins play key roles during the tumorigenesis of gastric cancer. To identify novel potential targets for gastric cancer, differential expressed proteins between gastric cancer and adjacent normal tissues were analyzed with proteomics and bioinformatics tool. METHODS: The differentially expressed proteins between gastric cancer and adjacent normal tissues were analyzed by Omicsbean (multi-omics data analysis tool). Cell viability was tested by CCK-8 assay. Flow cytometry was used to measure cell apoptosis and cycle. Transwell assay was used to test cell migration and invasion. Gene and protein expressions were detected by RT-qPCR, immunohistochemistry and Western blot, respectively. RESULTS: MAGOH and MAGOHB were found to be notably upregulated in gastric cancer tissues compared with that in normal tissues. Knockdown of MAGOH significantly inhibited the proliferation of gastric cancer cells via inducing the cell apoptosis. In addition, MAGOH knockdown induced G2 phase arrest in gastric cancer cells. Moreover, MAGOH knockdown notably inhibited migration and invasion of gastric cancer cells. Importantly, double knockdown of MAGOH and MAGOHB exhibited much better anti-tumor effects on gastric cancer compared with alone treatment. Finally, double knockdown of MAGOH and MAGOHB mediated the tumorigenesis of gastric cancer via regulation of RAF/MEK/ERK signaling. CONCLUSION: MAGOH knockdown inhibited the tumorigenesis of gastric cancer via mediation of b-RAF/MEK/ERK signaling, and double knockdown of MAGOH and MAGOHB exhibited much better anti-tumor effects. This finding might provide us a new strategy for the treatment of gastric cancer.