| Objective: Gastric cancer(GC)is still one of the most common and malignant tumors in the world.The 5-year survival rate for early gastric cancer can reach more than 90%,while the 5-year survival rate for advanced gastric cancer is often less than 20%.Unfortunately,most patients are diagnosed at an advanced stage.Since GC is a highly heterogeneous tumor,patients with GC benefits from chemotherapy,chemoradiotherapy,targeted therapy,and immunotherapy are very limited.Therefore,it is very meaningful to improve the overall prognosis and promote individualized precision treatment by further exploring the potential molecular mechanisms of GC,understanding the highly molecular heterogeneity of GC,finding new key molecules that play a central role in the occurrence and development of GC,and developing targeted drμgs targeting these molecular markers.SCNN1 G is a gene encoding the γ subunit of epithelial sodium channels.The effect of SCNN1 G on gastric cancer and the potential molecular mechanism behind these effects are still unclear.Materials and methods: In this study,we used real-time quantitative PCR(q RT-PCR),Western blot(Western blot)and immunohistochemistry to compare the differences about expression level between 35 cases of fresh gastric cancer tissue and adjacent cancer tissues at the m RNA level and protein level,respectively.And the relationship between SCNN1 G expression and GC survival or clinicopathological characteristics was further analyzed.In order to study the potential molecular mechanism of SCNN1 G involved into GC,we constructed a cell line with stable knockout and overexpression of SCNN1 G.Furthermore,we analyzed the regulation of SCNN1 G expression in vitro and in mice on the ability of proliferation and cloning,scratch healing and migration and invasion.In addition,we also explored the gastric cancer-related signaling pathways that SCNN1 G may participate in throμgh enrichment analysis of SCNN1G-related differential genes.Finally,we further verified the effect of SCNN1 G on the proliferation of GC by establishing a nude mouse subcutaneous tumor model and conducting an experiment in vivo.Results: After analysis,we found that SCNN1 G is significantly down regulated in GC tissue,and the prognosis of patients with high expression level of SCNN1 G is significantly prolonged(P=0.0088).Further analysis showed that SCNN1 G is an independent predictor of the prognosis of gastric cancer.In order to study the potential molecular mechanism of SCNN1 G affecting gastric cancer,we constructed a cell line with stable knockout and overexpression of SCNN1 G and found that SCNN1 G can significantly reduce the proliferation and cloning ability of gastric cancer cells,which was confirmed by experiments in mice.In addition,we also found that SCNN1 G can significantly inhibit the ability of proliferation and cloning,scratch healing and migration and invasion.Interestingly,throμgh differential expressed gene enrichment analysis,we found that the expression of SCNN1 G is closely related to the WNT/β-catenin signaling pathway.In GC cell lines,the expression of SCNN1 G was significantly negatively correlated with the expression of β-catenin,and the downstream target molecules of the WNT/β-catenin pathway,c-myc,cyclin D1,and Axin2,in the SCNN1 G overexpression group were also significantly down-regulated.Finally,we further verified the effect of SCNN1 G on the proliferation of gastric cancer throμgh the establishment of a nude mouse subcutaneous tumor model and found that the tumor proliferation of the SCNN1 G high expression group was significantly restricted.Conclusion: We found that SCNN1 G is a novel prognostic factor with independent predictive value for gastric cancer,and it is significantly down-regulated in gastric cancer tissues.And SCNN1 G may act as a new component to mediate the occurrence,proliferation and metastasis of gastric cancer by regulating the Wnt/β-catenin pathway. |
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