幽门螺杆菌对胃癌患者微小核糖核酸-146、人类表皮生长因子受体2表达影响研究

Effect of Helicobacter pylori on the expression of microRNA-146 and human epidermal growth factor receptor 2 in patients with gastric cancer

目的探讨幽门螺杆菌对胃癌患者微小核糖核酸-146(miR-146)、人类表皮生长因子受体2(HER2)表达的影响。方法选取自2018年1月至2018年12月收治的54例胃癌患者为研究对象,根据幽门螺杆菌感染情况分为阴性组(n=16)与阳性组(n=38)。收集胃癌患者胃黏膜标本,实时定量聚合酶链式反应检测标本中miR-146、HER2的表达水平,免疫印迹试验检测HER2蛋白表达水平。培养人胃腺癌细胞,加入幽门螺杆菌,并分别转染miR-146 mimic、miR-146 inhibitor,检测miR-146被抑制前后HER2的表达。结果阳性组患者HER2的mRNA和蛋白表达水平均较阴性组显著上调,miR-146表达较阴性组显著上调,差异有统计学意义(P<0.05)。阳性组患者HER2的mRNA的表达水平与miR-146表达水平呈正相关(r=0.485,P<0.05)。癌细胞经幽门螺杆菌刺激后,HER2的mRNA及蛋白表达均较刺激前显著上调;转染miR-146a mimic、miR-146b mimic、miR-146a/b mimic后,HER2的mRNA及蛋白表达较转染前显著上调;转染miR-146a inhibitor、miR-146b inhibitor、miR-146a/b inhibitor后,HER2的mRNA及蛋白表达较转染前显著下降,差异均有统计学意义(P<0.05)。结论在幽门螺杆菌阳性的胃癌患者中,幽门螺杆菌可能通过促进miR146介导上调HER2表达。

Objective To investigate the effect of Helicobacter pylori on the expression of microRNA-146(miR-146)and human epidermal growth factor receptor 2(HER2)in patients with gastric cancer.Methods A retrospective study was performed on 54 cases of patients with gastric cancer who were admitted from January 2018 to December 2018.According to the situation of Helicobacter pylori infection,patients were divided into the negative group(n=16)and positive group(n=38).Gastric mucosa samples of patients with gastric cancer were collected,and the expression levels of miR-146 and HER2 in the samples were detected by real-time quantitative polymerase chain reaction,and the protein expression levels of HER2 were detected by Western blot assay.Human gastric adenocarcinoma cells were cultured,Helicobacter pylori was added,and transfected with miR-146 mimic and miR-146 inhibitor,respectively,to detect the expression of HER2 before and after miR-146 inhibition.Results The expression levels of HER2 mRNA and protein in the positive group were significantly up-regulated compared with the negative group,and the expression of miR-146 was significantly up-regulated compared with the negative group,with statistical significance(P<0.05).The expression level of HER2 mRNA in the positive group was positively correlated with the expression level of miR-146(r=0.485,P<0.05).The mRNA and protein expression of HER2 were significantly up-regulated after Helicobacter pylori stimulation.After transfection with miR-146a mimic,miR-146b mimic and miR-146a/b mimic,the mRNA and protein expressions of HER2 were significantly up-regulated compared with those before transfection.After transfection with miR-146a inhibitor,miR-146b inhibitor and miR-146a/b inhibitor,the mRNA and protein expressions of HER2 were significantly reduced compared with before transfection,with statistically significant difference(P<0.05).Conclusion In gastric cancer patients with positive Helicobacter pylori,Helicobacter pylori may up regulate HER2 expression by promoting mir146.