组蛋白甲基转移酶NSD3对肾癌细胞增殖、侵袭及迁移的影响  

Effect of histone methyltransferase NSD3 on the proliferation,invasion,and migration of renal cancer cells

作　　者：韩勖 罗凤宝 马旭怡[1] HAN Xu;LUO Fengbao;MA Xuyi(Department of Urology,First People’s Hospital of Changzhou,Changzhou Jiangsu 213003,China)

机构地区：[1]常州市第一人民医院泌尿外科,江苏常州213003

出　　处：《临床与病理杂志》2023年第12期2063-2070,共8页Journal of Clinical and Pathological Research

基　　金：江苏省双创博士基金(JSSCBS20211591)。

摘　　要：目的:组蛋白甲基转移酶——variegation,zeste增强子和trithorax域3的核受体抑制剂(nuclear receptor suppressor of variegation,enhancer of zeste,and trithorax domain-containing 3,NSD3)在肾癌中的生物学作用还不清楚。本研究旨在探讨NSD3在肾癌组织和细胞中的表达,以及其对肾癌细胞增殖、侵袭及迁移的影响和潜在的分子机制。方法:下载高通量基因表达综合(Gene Expression Omnibus,GEO)数据库中的基因芯片数据,对其进行二次分析,比较NSD3 mRNA在正常肾组织与肾癌组织中的表达差异。采用实时聚合酶链反应和蛋白质印迹法检测NSD3在正常肾小管上皮HK-2细胞与肾癌786-O细胞中的表达以及NSD3小干扰RNAs(small interfering RNAs,siRNAs)在肾癌786-O细胞中的敲减效率。通过细胞计数试剂盒8(cell counting kit-8,CCK-8)实验、Transwell侵袭实验、Transwell迁移实验检测下调NSD3对肾癌786-O细胞增殖、侵袭及迁移的影响。通过蛋白质印迹法检测细胞外信号调节蛋白激酶1/2(extracellular signal-regulated protein kinases 1/2,ERK1/2)信号通路的激活、基质金属蛋白酶(matrix metallopeptidase,MMP)2和MMP9的表达水平。结果:与正常肾组织和细胞相比,NSD3在肾癌组织和细胞中的表达水平均升高(均P<0.05)。转染siRNAs下调NSD3表达能够减弱肾癌786-O细胞的增殖、侵袭与迁移能力(均P<0.05);同时抑制ERK1/2信号通路激活,并降低MMP2和MMP9蛋白表达(均P<0.05)。结论:NSD3可能通过调控ERK1/2信号通路促进肾癌细胞增殖、侵袭及迁移。Objective:The biological role of histone methyltransferase nuclear receptor suppressor of variegation,enhancer of zeste,and trithorax domain-containing 3(NSD3)in renal cancer remains unclear.This study aims to investigate the expression of NSD3 in renal cancer tissues and cells,as well as its effects on proliferation,invasion,and migration of renal cancer cells and the potential molecular mechanisms involved.Methods:The secondary analysis was performed to compare the differential expression of NSD3 mRNA between normal kidney tissues and renal cancer tissues on the gene chip data downloaded from the Gene Expression Omnibus(GEO)database.Real-time polymerase chain reaction(real-time PCR)and Western blotting were performed to detect the expression of NSD3 in normal renal tubular epithelial HK-2 cells and renal cancer 786-O cells,as well as the knockdown efficiency of NSD3 small interfering RNAs(siRNAs)in 786-O cells.The effects of NSD3 downregulation on proliferation,invasion,and migration of 786-O cells were detected by cell counting kit-8(CCK-8)assay,Transwell invasion assay,and Transwell migration assay.The activation of extracellular signal-regulated protein kinases 1/2(ERK1/2)signaling pathway and the expression levels of matrix metallopeptidase(MMP)2 and MMP9 protein were determined by Western blotting assay.Results:Compared with normal kidney tissues and cells,NSD3 expression was increased in renal cancer tissues and cells(both P<0.05).Transfection with NSD3 siRNAs to knockdown NSD3 expression weakened the proliferation,invasion,and migration abilities of 786-O cells(all P<0.05),inhibited the activation of ERK1/2 signaling pathway,and decreased the expression levels of MMP2 and MMP9 protein(all P<0.05).Conclusion:NSD3 may promote cell proliferation,invasion,and migration of renal cancer cells by regulating the ERK1/2 signaling pathway.

关 键 词：组蛋白甲基转移酶 variegation zeste增强子和trithorax域3的核受体抑制剂 肾癌 增殖 侵袭 迁移 

分 类 号：R737.11[医药卫生—肿瘤]