promotes the progression of gastric cancer through the focal adhesion kinase/phosphatidyl-inositol-3-kinase/protein kinase B pathway and epithelial-mesenchymal transition.

Background: Regulator of G protein signaling (RGS) proteins participate in tumor formation and metastasis by acting on the α-subunit of heterotrimeric G proteins. The specific effect of RGS, particularly , on the progression of gastric cancer (GC) is not yet clear.

Aim: To explore the role and underlying mechanisms of action of in GC development.

Methods: The prognostic significance of in GC was analyzed using bioinformatics based public databases and verified by immunohistochemistry and quantitative polymerase chain reaction in 90 patients with GC. Function assays were employed to assess the carcinogenic impact of , and the mechanism of its possible influence was detected by western blot analysis. A nude mouse xenograft model was established to study the effects of on GC growth .

Results: was highly expressed in GC tissues compared with matched adjacent normal tissues. Elevated expression was correlated with increased tumor-node-metastasis stage, increased tumor grade as well as poorer overall survival in patients with GC. Cell experiments demonstrated that knockdown suppressed GC cell proliferation, migration and invasion. Similarly, xenograft experiments confirmed that RGS4 silencing significantly inhibited tumor growth. Moreover, RGS4 knockdown resulted in reduced phosphorylation levels of focal adhesion kinase, phosphatidyl-inositol-3-kinase, and protein kinase B, decreased vimentin and N-cadherin, and elevated E-cadherin.

Conclusion: High expression in GC indicates a worse prognosis and is a prognostic marker. influences tumor progression the focal adhesion kinase/phosphatidyl-inositol-3-kinase/protein kinase B pathway and epithelial-mesenchymal transition.