Objective:This stndy aims to investigate whether the inhibition of protein phosphatase 2A catalytic subunit Cα(PP2Acα) affects the malignant phenotype of gastric cancer cells and the expression of Wilms tumor 1 related protein(WTAP) in this progression. Methods:The Cancer Genome Atlas(TCGA)database was used to compare the expression of PP2Acα coding gene(PPP2CA)and WTAP in gastric cancer and normal tissues adjacent to the cancer;the KM-plot website was used to analyze the relationship between PPP2CA,WTAP and the prognosis of gastric cancer;lentivirus-mediated short hair Card RNA(shRNA)was used to inhibit the expression of PP2Acα in gastric cancer cells,and then RNA and protein for PCR and WB were extracted to detect the mRNA and protein levels of PPP2CA/PP2Acα and WTAP,respecfively;finally,the influences of PP2Acα inhibition on gastric cancer cells phenotype were detected in vitro and in vivo. Results:After inhibiting PP2Acα,it was found that the proliferation,migration and invasion capabilities of gastric cancer cells were enhanced with epithelial-mesenchymal transition(EMT),accompanied by a significant increase in the protein levels of WTAP. Conclusion:Inhibition of PP2Acɑ promotes the malignant phenotype of gastric cancer cells,which may be achieved by upregulating the levels of WTAP.