TRIM37在肝癌中的表达及其对肝癌细胞增殖、侵袭及迁移的影响

Th e expression of TRIM37 in liver cancer and its effects on the proliferation,invasion,and migration of liver cancer cells

目的探讨三结构域蛋白37(TRIM37)在肝癌中的表达及其对肝癌细胞增殖、侵袭及迁移的影响。方法采用生物信息学分析癌症基因组图谱数据库中肝癌TRIM37 mRNA表达水平及其对患者生存的影响。采用蛋白免疫印迹法(WB)试验检测肝癌组织和癌旁正常组织中TRIM37蛋白的表达。采用RNA干扰技术将特异性靶向TRIM37、非靶向对照的siRNA作用于Huh7细胞,分为敲低组(siTRIM37#1组、si-TRIM37#2组)和非靶向对照组(si-NC组)。采用Transwell迁移实验检测细胞迁移能力。采用WB试验检测细胞TRIM37蛋白及上皮-间质转化(EMT)相关标志蛋白表达,以及PTEN/AKT/GSK-3β/β-catenin信号通路相关蛋白的表达。结果生物信息学分析结果显示,肝癌组织TRIM37 mRNA表达高于癌旁正常组织(P<0.05);生存分析显示,高表达TRIM37患者总生存期低于低表达TRIM37患者(P<0.05)。si-TRIM37组细胞的侵袭能力低于si-NC组(P<0.05);si-TRIM37组N-cadherin、Vimentin蛋白表达量比si-NC组下降(P<0.05),E-cadherin蛋白表达量增加(P<0.05);si-TRIM37组比si-NC组P-AKT、P-GSK-3β、β-catenin蛋白表达量下降(P<0.05),PTEN蛋白表达量升高(P<0.05)。结论TRIM37在人肝癌组织中高表达,并与患者预后相关。敲低TRIM37抑制肝癌细胞EMT标记蛋白的表达,并抑制细胞的侵袭,可能与抑制PTEN/AKT/GSK-3β/β-catenin信号通路有关。

Objective To examine the expression of TRIM37 in liver cancer and its influence on the migration of liver cancer cells,as well as to investigate the underlying mechanism of its action.Methods The expression level of TRIM37 mRNA in liver cancer and its correlation with patient survival in the cancer genome atlas database were analyzed using bioinformatics.Additionally,the expression level of TRIM37 protein in liver cancer tissue and adjacent normal tissue was detected through protein immunoblotting(WB).Furthermore,RNA interference technology was employed to apply siRNAs targeting TRIM37 and non-targeted Controls to Huh7 cells,which were divided into a knockdown group(si-TRIM37#1 group,si-TRIM37#2 group)and a non-targeted control group(si-control group).The Transwell migration assay was employed to assess the migration capacity of cells.WB was used to detect the expression of cellular TRIM37 protein and epithelial-mesenchymal transition(EMT)-related marker proteins,as well as the expression of proteins related to PTEN/AKT/GSK-3β/β-catenin signaling pathway.Results Bioinformatics analysis showed that TRIM37 was highly expressed in liver cancer tissue compared to normal tissue adjacent to cancer(P<0.05).Survival analysis showed that the overall survival of patients with high expression of TRIM37 was lower than that of patients with low expression of TRIM37(P<0.05).The Transwell invasion experiment showed that the invasive ability of cells in the si TRIM37 group was significantly lower than that in the si NC group(P<0.05).The WB method showed that the expression levels of N-cadherin and Vimentin proteins in the si-TRIM37 group decreased compared to the si-NC group,while the expression levels of E-cadherin proteins increased,with statistical significance(P<0.05).The si-TRIM37 group exhibited a significant decrease in the expression levels of P-AKT,β-catenin,and P-GSK-3βcompared to the si-NC group(P<0.05).Conversely,PTEN protein expression showed a significant increase(P<0.05).Conclusion The expression of the TRIM37 gene is significantly elevated in human liver cancer tissue and exhibits a negative correlation with patient prognosis.Suppression of TRIM37 resulted in the downregulation of EMT marker proteins in liver cancer cells and hindered cell invasion,potentially through the inhibition of the PTEN/AKT/GSK-3β/β-catenin signaling pathway.