胃癌中TRIM11的表达及其对PI3K/Akt信号通路的影响

Clinical significance of tripartite motif containing 11 expression in gastric cancer and its effect on the proliferation and apoptosis of gastric cancer cells

目的探讨胃癌组织中三结构域蛋白11(tripartite motif containing 11,TRIM11)的表达及其对胃癌细胞PI3K/Akt信号通路的影响。方法收集120例行手术切除的胃癌组织和对应癌旁组织,采用qRT-PCR和免疫组化法检测胃癌组织和癌旁组织中TRIM11 mRNA和蛋白的表达水平,并分析TRIM11 mRNA表达与胃癌临床病理特征的相关性。体外培养胃癌细胞系AGS,转染TRIM11-siRNA 24 h后,EdU检测胃癌细胞增殖情况,流式细胞仪检测胃癌细胞凋亡情况,Western blot法检测PI3K/Akt信号通路相关蛋白表达变化。结果癌旁组织中TRIM11阳性率为11.7%(14/120),胃癌组织中TRIM11阳性率为80.8%(97/120),差异有统计学意义(P<0.01),且TRIM11表达与胃癌临床分期、浸润深度、淋巴结转移相关(P<0.05)。与正常胃黏膜上皮细胞相比,胃癌细胞中TRIM11 mRNA表达升高(P<0.01)。与Control组相比,TRIM11-siRNA组胃癌细胞的增殖显著降低(P<0.01),凋亡指数升高(P<0.01),p-PI3K/PI3K、p-Akt/Akt蛋白表达均显著降低(P<0.01),转染TRIM11-NC组无显著变化。结论胃癌组织中TRIM11高表达,且与胃癌的恶性病理因素相关;TRIM11-siRNA能够抑制胃癌细胞增殖,促进细胞凋亡,其机制与PI3K/Akt信号通路相关。

Purpose To explore the expression of tripartite motif containing 11(TRIM11)protein in the tissues of gastric cancer patients and its effect on the PI3K/Akt signaling pathway of gastric cancer cells.Methods A total of 120 cases of gastric cancer tissues and adjacent tissues were collected.qRT-PCR and immunohistochemistry were used to detect the expression levels of TRIM11 mRNA and protein in gastric cancer tissues and adjacent tissues.The chi-square test was used to analyze the expression levels of TRIM11 mRNA and its correlation of clinicopathologic characteristics in patients with gastric cancer.24 hours after transfection of TRIM11 siRNA into gastric cancer cell line AGS cultured in vitro,EdU assay was used to show gastric cancer cell proliferation,flow cytometry was used to detect gastric cancer cell apoptosis.Western blot analysis was used to detect the expression of key proteins in the PI3K/Akt signaling pathway.Results The proportion of TRIM11-positive cells in paracancerous tissue was 11.7%(14/120),and that in gastric cancer tissue was 80.8%(97/120),and the difference was statistically significant(P<0.01).And it was significantly correlated with clinical stage,degree of infiltration and lymph node metastasis of gastric cancer patients(P<0.05).Compared with normal gastric mucosa epithelial cells,gastric cancer cells had higher TRIM11 mRNA expression(P<0.01).Compared with the control group,the proliferation of gastric cancer cells in the TRIM11 siRNA group was significantly reduced(P<0.01),the apoptotic index was increased(P<0.01),and the expression of p-PI3K and p-Akt proteins was significantly decreased(P<0.01).There was no significant change in the TRIM11-NC transfected group.Conclusion TRIM11 is highly expressed in gastric cancer tissues and related to the malignant pathological factors of gastric cancer.TRIM11-siRNA can inhibit the proliferation of gastric cancer cells and promote cell apoptosis,and its mechanism is related to the PI3K/Akt signaling pathway.