高迁移率族蛋白B1基因沉默抑制子宫内膜癌侵袭与转移的机制  

Mechanism of inhibitory effects of silencing high mobility group box-1 on invasion and migration of endometrial carcinoma of uterus

作　　者：刘心怡[1] 吴佳捷[1] 

机构地区：[1]中南大学湘雅医院妇产科,长沙410008

出　　处：《中南大学学报（医学版）》2016年第3期251-257,共7页Journal of Central South University ：Medical Science

基　　金：湖南省科学技术厅科技计划一般项目(2014K3125)~~

摘　　要：目的:探讨小干扰RNA抑制高迁移率族蛋白B1(high mobility group box-1,HMGB1)表达后对p38MAPK通路的影响,从而了解HMGB1影响子宫内膜癌侵袭与转移的机制。方法:运用RNA干扰技术,设计合成4条HMGB1sh RNA,将HMGB1沉默效果最好的HMGB1 sh RNA转染子宫内膜癌HEC-1A细胞,通过RT-PCR和Western印迹技术检测转染后细胞HMGB1及p38MAPK在基因和蛋白水平的表达情况,MTT实验检测转染后细胞生长活力状态。结果:RTPCR和Western印迹结果均证实HMGB1 sh RNA载体成功抑制HMGB1和p38MAPK在HEC-1A细胞中m RNA和蛋白的表达(P<0.05);MTT结果显示HMGB1 sh RNA转染后HEC-1A细胞生长明显受抑(P<0.05)。结论:HMGB1表达下调可有效抑制子宫内膜癌细胞HEC-1A的增殖、侵袭和转移,此过程可能通过p38MAPK信号通路进行调节。Objective： To determine the effects of p38 mitogen-activated protein kinase（MAPK） signal pathway after small hairpin RNA on inhibiting the expression of high mobility group box-1（HMGB1）, and to explore the mechanism responsible for the effects of HMGB1 on invasion and migration of endometrial carcinoma of uterus.Methods： Based on RNA interference technology, we designed and synthetized HMGB1 small hairpin RNA（HMGB1 sh RNA-1, HMGB1 sh RNA-2, HMGB1 sh RNA-3, HMGB1 sh RNA-1）, and then transfected HMGB1 sh RNA plasmids into HEC-1A cells. The expression of genes and proteins was examined by RT-PCR and Western blot. The activity of HEC-1A cells was evaluatedby the methyl thiazolyl tetrazolium（MTT） method.Results： HMGB1 sh RNA effectively inhibited the expression of the HMGB1 and p38 MAPK in HEC-1A cells（P〈0.05）. Among the sh RNAs, the inhibitory effect of HMGB1 sh RNA-3 was the best（P〈0.05）. According to the results of MTT, the growth of HEC-1A cells was obviously inhibited after transfection of HEC-1A HMGB1 sh RNA（P〈0.05）. Conclusion： Downregulation of HMGB1 may effectively inhibit proliferation, invasion and migration of HEC-1A cells in endometrial carcinoma of uterus, which is dependent on p38 MAPK signal pathway.

关 键 词：高迁移率族蛋白B1 RNA干扰 子宫内膜癌细胞 P38丝裂原活化蛋白激酶 

分 类 号：R737.33[医药卫生—肿瘤]