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Objective To investigate the effects of silencing axon guide protein 4D (Sema4D) on the growth, autophagy and epithelial-mesenchymal transformation of gastric cancer cell SGC-7901. Methods The cells were randomly divided into control group, shRNA-NC group, Sema4D-shRNA1 group, Sema4D-shRNA2 group and Sema4D-shRNA3 group, and transfected into SGC-7901 with shRNA Sema4D vector. The expression of Sema4D mRNA was detected by RT-PCR. The clone formation rate was determined by colony formation assay. Flow cytometry was used to detect apoptosis. Morphological changes of epithelialmesenchymal transformation were observed microscopically. Western blotting was used to detect the expression levels of Ki67, proliferating cell nuclear antigen (PCNA), Bax, Bcl-2, caspase-3, cleaved caspase-3, Beclin1, p62, LC3Ⅰ, LC3Ⅱ, E-cadherin, N-cadherin, and vimentin proteins. Results The results of RT-PCR showed that compared with the control group, the mRNA levels of Sema4D-shRNA1 group, Sema4D-shRNA2 group and Sema4D-shRNA3 group were significantly lower, and the mRNA level of Sema4D-shRNA3 group was significantly lower than that of Sema4D-shRNA1 group and Sema4D-shRNA2 group (P |