连接粘连分子3对肾癌细胞迁徙和凋亡的作用机制  

Junctional adhesion molecules regulate migration and apoptosis of renal cell carcinoma

作　　者：王志刚[1] 李燕[1] 孙吉平[1] 余晓洋[1] 张文静[1] 吕佳 邵耀中[1] 张亚莉[1] 李旭东[2] WANG Zhi-gang;LI Yan;SUN Ji-ping;YU Xiao-yang;ZHANG Wen-jing;LV Jia;SHAO Yao-zhong;ZHANG Ya-li;LI Xu-dong(Department of Nephrology,Kidney Hospital,Xi'an 710061;Department of Urology,First Hospital of Xi'an Jiaotong University,Xi'an 710061,China)

机构地区：[1]西安交通大学第一附属医院肾脏病医院肾脏内科,陕西西安710061 [2]西安交通大学第一附属医院泌尿外科,陕西西安710061

出　　处：《现代泌尿外科杂志》2020年第3期252-257,共6页Journal of Modern Urology

摘　　要：目的研究连接粘附分子3(JAM3)在肾癌细胞中的表达情况以及在调控肾癌细胞迁徙和凋亡过程中的可能作用及机制。方法①RT-qPCR和Western-blot检测JAM3的表达水平;②siRNA、流式细胞仪、细胞划痕实验及细胞迁移实验分析其对RCC迁移和凋亡的影响;③Western-blot检测E-钙粘蛋白、N-钙粘蛋白、整合素β1和基质金属蛋白酶2(MMP-2)表达水平,初步探究JAM3影响癌细胞迁移的可能机制。结果①与正常肾小管上皮细胞相比,人肾癌细胞中的JAM3表达显著上调(P<0.05);②JAM3敲除可促进肾癌细胞的凋亡(P<0.05)及抑制肾癌细胞迁移(P<0.05);③JAM3基因敲除后,肾癌细胞中E-粘连蛋白的表达增加,N-粘连蛋白、整合素β1、MMP-2、Bcl-2的蛋白水平下降(P<0.05)。结论 RCC中JAM3表达上调,并可能通过调控E-钙粘蛋白、N-钙粘蛋白、整合素β1、MMP-2表达水平抑制癌细胞凋亡和促进其迁移。Objective To investigate the expression of junctional adhesion molecule 3(JAM3) in renal cell carcinoma(RCC),and to explore the mechanism of regulating renal cell migration and apoptosis.Methods The mRNA and protein expressions of JAM3 were detected with reverse transcription-polymerase chain reaction(RT-qPCR) and Western blotting.The effects of JAM3 on the migration and apoptosis of RCC cells were analyzed using siRNA,flow cytometry,wound healing assay and cell migration assay.The expressions of E-cadherin,N-cadherin,integrin β1 and matrix metalloproteinase-2(MMP-2) were detected with Western blotting to analyze the mechanism of JAM3’s effects on cancer cell migration.Results Compared with normal renal tubular epithelial cells,RCC cells had significantly up-regulated JAM3 expression(P<0.05).JAM3 knockdown promoted RCC cell apoptosis(P<0.05) and inhibited the migration(P<0.05).JAM3 gene silence increased expression of Ecadherin,but decreased expressions of N-cadherin,integrin β1,MMP-2 and Bcl-2(P<0.05).Conclusion JAM3 expression is uprregulated in RCC cells.JAM3 may inhibit cancer cell apoptosis and promote the migration by regulating E-cadherin,N-cadherin,integrin β1 and MMP-2 levels.

关 键 词：肾细胞癌 连接粘附分子3 E-钙粘蛋 N-钙粘蛋白 整合素Β1 基质金属蛋白酶2 

分 类 号：R692.9[医药卫生—泌尿科学]