PSME1/2通过抑制CDK15的表达促进子宫内膜癌细胞的增殖和侵袭

Proteasome activator subunit 1/2 promotes the proliferation and invasion of endometrial carcinoma cells by inhibiting the expression of cyclin-dependent kinase 15

摘要:

目的 探索人类蛋白酶体激活剂（proteasome activator subunit，PSME）1/2在子宫内膜癌（endometrial carcinoma，EC）中的表达水平及其对EC细胞增殖和侵袭的影响。方法 检测子宫内膜细胞系和原代细胞中PSME1/2和细胞周期蛋白依赖性激酶15（cyclin-dependentkinase 15，CDK15）的表达，以敲低株分析PSME1/2与CDK15的表达相关性及其对肿瘤增殖和侵袭影响。比较PSME1/2和CDK15在EC组织和癌旁组织中的表达水平差异，并分析其对EC患者预后的影响。结果 与人正常子宫内膜细胞系相比，PMSE1/2在HEC1B（human endometrial adenocarcinoma cells，HEC1B）及原代细胞中mRNA（messenger RNA，mRNA）高表达和蛋白高表达，CDK15蛋白表达量下降。与对照组和双敲组比，CDK15在HEC1B系PSME1/2敲低株的蛋白表达升高，提示CDK15可能受PSME1/2抑制。在EC组织PMSE1/2高表达，CDK15低表达。PSME1/2表达与患者临床资料如年龄、术后诊断分型、分化程度、术后分期等差异无统计学意义（P>0.05）。PSME1/2、CDK15的表达与EC患者的不良预后无明显相关性（P>0.05）。结论 PSME1/2抑制CDK15的表达而促进EC细胞的增殖和侵袭，PSME1/2具有促EC作用。

Abstract:

Objective To investigate the expression level of proteasome activator subunit 1/2（PSME1/2） in endometrial carcinoma and its effect on the proliferation and invasion of endometrial carcinoma cells.Methods The expression levels of PSME1/2 and cyclin-dependent kinase 15（CDK15） were measured in endometrial cell lines and primary cultured cells，and knock-down strains were used to analyze the correlation between PSME1/2 and CDK15 and the effect of PSME1/2 on tumor proliferation and invasion. The expression levels of PSME1/2 and CDK15 were compared between endometrial carcinoma tissue and paracancerous tissue，and the influence of PSME1/2 and CDK15 on the prognosis of patients with endometrial carcinoma was analyzed.Results Compared with normal human endometrial cell lines，human endometrial adenocarcinoma HEC1B cells and primary cultured cells had high mRNA and protein expression levels of PMSE1/2 and a reduction in the protein expression of CDK15. Compared with the control group and the double knock-down group，there was an increase in the protein expression level of CDK15 in the HEC1B line with PSME1/2 knock-down，suggesting that CDK15 might be inhibited by PSME1/2. There was a high expression level of PMSE1/2 and a low expression level of CDK15 in endometrial carcinoma. There were no significant differences in age，postoperative diagnosis and typing，degree of tumor differentiation，and postoperative stage between the high PSME1/2 expression group and the low PSME1/2 expression group（P>0.05）. There was no significant correlation between the expression of PSME1/2 and CDK15 and the poor prognosis of patients with endometrial carcinoma（P>0.05）.Conclusion PSME1/2 can inhibit the expression of CDK15 and promote the proliferation and invasion of endometrial carcinoma cells，and PSME1/2 can also promote endometrial carcinoma.