SMC4 promotes the progression of cardia adenocarcinoma via regulation of the Wnt/β-catenin signaling pathway

Abstract Background: Structural maintenance of chromosome protein 4 (SMC4) is crucial for chromosome assembly and separation, but its role and mechanism in cardia adenocarcinoma (CA) are unknown.Methods: SMC4 expression levels were initially detected by protein profiling in 20 CA tumour tissues and adjacent normal tissues. The level of SMC4 expression in CA was then evaluated using a Western Blot analysis. Cell proliferation was evaluated by CCK-8 and clone formation test, Scratch and transwell tests were used to investigate cell migration as well as invasion, while through the flow cytometry, we examined the cell apoptosis and progression of the cell cycle. The regulatory effects of the epithelial-mesenchymal transition (EMT) and the Wnt/β-catenin pathway were investigated using Western Blot. A tumorigenesis experiment was used to investigate the influence of SMC4 on tumor development in nude mice.Results: This study showed overexpression of SMC4 in CA tissues and cells. SMC4 knockout significantly caused the inhibition of proliferation, migration, and invasion of CA cells, and inhibited tumor growth in vivo by stimulating the apoptosis and cell cycle arrest in the G0/G1 phase, In addition, down-regulation of SMC4 resulted in decreased expression of Bcl-2, Cyclin D1, CDK4, CDK6, β-catenin, phosphorylated GSK-3β, N-cadherin, and Vimentin, with an increased level of proteins i.e Bax, cleaved-caspase3, and E-cadherin. When SMC4 was overexpressed, these effects were reversed.Conclusion: SMC4 can facilitate the biological progression of CA, suggesting that SMC4 could be a potential therapeutic target for the disease.An earlier version of our study has been presented as a preprint in the following link: https://www.researchsquare.com/article/rs-698892/v1.