Induces Cell Proliferation in Cardia Adenocarcinoma via PI3K/AKT Signaling Pathway.

PURPOSE

Previous studies have shown that non-SMC condensin I complex subunit G () overexpression is correlated to poor prognosis of multiple cancer types. Herein, we explored the underlying mechanism of -mediated cardia adenocarcinoma (CA) proliferation and cell cycle regulation.

METHODS

The protein profiling technology was used to analyze the gene expression in 20 CA and adjacent tissue samples. Differential genes were identified by bioinformatic analysis. Western blot and qRT-PCR-based analysis assessed the expression levels in multiple CA cell lines. CA cell lines, SGC-7901 and AGS, were transfected with Lip 2000, and stably transfected cell lines were screened for overexpression and downregulation. MTT and clone formation assays were employed to detect cell proliferation, and cell cycle phases were analyzed using flow cytometry. Western blot was performed to determine the gene expression levels. Finally, we studied the tumorigenic effects of in the mouse model and validated the cell experiment results using immunohistochemistry.

RESULTS

A significant overexpression of was found in CA tissues and CA cell lines. The outcomes of MTT and clone formation assays showed that upregulation promoted cell proliferation. The outcomes of these analyses were further validated using nude mice as an in vivo tumor model. As per the outcome of Western blot and flow cytometry analysis, regulated the G1 phase through the cyclins (CDK4, CDK6, and cyclin D1) overexpression and cell cycle inhibitors (P21 and P27) downregulation. Overexpressed and silenced , both in vitro and in vivo, resulted in abnormal activation of the PI3K/AKT signaling pathway in CA cells. We observed that overexpression increased the levels of phosphorylated PI3K, AKT, and GSK3β; however, their total protein levels remained unchanged in CA cells.

CONCLUSION

As a CA oncogene, promoted cell proliferation and regulated cell cycle through PI3K/AKT signaling pathway activation.