SERINC2通过激活TGF-β/Smad3信号通路促进脑胶质瘤细胞的迁移和侵袭

The migration and invasion of giloma cells promoted by SERINC2 through activating the TGF-β/Smad3 signaling pathway

目的探讨丝氨酸整合因子2(Serine incorporator 2,SERINC2)对脑胶质瘤细胞迁移和侵袭的影响及相关分子机制。方法利用GEPIA数据库在线分析脑胶质瘤组织和正常脑组织中SERINC2的表达差异;运用CGGA数据库检测SERINC2 mRNA的表达水平与脑胶质瘤患者生存率的关系;利用shRNA构建敲低SERINC2的U251细胞株,qRTPCR和Western blot检测敲低效率;采用划痕实验、Transwell实验分别检测SERINC2对U251细胞迁移和侵袭能力的影响;Western blot检测上皮-间质转化(EMT)和转化生长因子-β(TGF-β)/Smad3通路相关蛋白的表达。结果SERINC2 mRNA在脑胶质瘤中的表达高于正常脑组织,且SERINC2 mRNA高表达患者的10年生存率明显低于低表达患者(P<0.05);与对照组相比,敲低SERINC2后U251细胞的迁移和侵袭能力下降(P<0.05),且E-cadherin蛋白表达水平上升,TGF-β、Smad2/Smad3、p-Smad3和N-cadherin蛋白表达水平下降。结论SERINC2在脑胶质瘤中高表达,并且通过激活TGF-β/Smad3信号通路影响脑胶质瘤细胞EMT,从而促进脑胶质瘤细胞的迁移和侵袭。

Objective To investigate the effects of serine incorporated 2(SERINC2)on the migration and invasion of glioma cells and its related molecular mechanisms.Methods The GEPIA database was used to analyze the differential expression of SERINC2 mRNA between glioma tissue and normal brain tissue.CGGA database was used to detect the relationship between the expression level of SERINC2 mRNA and the survival rate of glioma patients.shRNA was used to construct U251 cell lines knockdown of SERINC2.qRT-PCR and Western blot were used to detect knockdown efficiency.The effects of SERINC2 on the migration and invasion ability of U251 cells were detected by scratch assay and Transwell assay,respectively.Western blot was used to detect the expression of epithelial mesenchymal transition(EMT)and TGF-β/Smad3 pathway related proteins.Results The expression of SERINC2 mRNA in glioma tissue was higher than that in normal brain tissue,and the 10-year survival rate of patients with high expression of SERINC2 mRNA was significantly lower than that of patients with low expression(P<0.05);Compared with the control group,the migration and invasion ability of U251 cells decreased after knockdown SERINC2(P<0.05),and the expression level of E-cadherin protein increased,while the expression levels of TGF-β,Smad2/Smad3,p-Smad3 and N-cadherin proteins decreased.Conclusion SERINC2 is highly expressed in gliomas.It affects the EMT of glioma cells by activating the TGF-β/Smad3 signaling pathway and promotes the migration and invasion of glioma cells.