沉默miR-572经铁死亡在肾癌细胞凋亡、索拉非尼耐药中的作用机制  

Effect of silencing miR-572 via ferroptosis on apoptosis and sorafenib resistance of renal cell carcinoma cells

作　　者：潘亮 畅雅学[1] 段万里[1] 邓骞 PAN Liang;CHANG Yaxue;DUAN Wanli(Department of Urology,Shaanxi Provincial People’s Hospital,Shaanxi,Xi’an 710061,China)

机构地区：[1]陕西省人民医院泌尿外科,西安市710061

出　　处：《河北医药》2024年第5期693-696,共4页Hebei Medical Journal

基　　金：陕西省自然科学基础研究计划(编号:2021JQ-910)。

摘　　要：目的探究沉默微小RNA-572(microRNA-572,miR-572)经铁死亡在肾癌细胞凋亡、索拉非尼耐药中的作用。方法购买人肾癌细胞系786-0,常规培养后分为空白组、过表达组、沉默组,空白组、过表达组、沉默组分别加入常规细胞培养液做空白处理,miR-572过表达质粒、Lipofectamine 2000试剂行过表达转染,miR-572 siRNA、Lipofectamine 2000试剂行沉默转染,随后建立3组细胞耐药细胞株。观察各组细胞miR-572表达量、细胞凋亡、索拉非尼耐药性及p53-SAT1-ALOX15信号通路蛋白表达量。结果与过表达组比较,沉默组miR-572表达量较低(P<0.05)。与过表达组比较,沉默组24 h、48 h肾癌细胞凋亡率较高(P<0.05)。与过表达组比较,沉默组IC50相对值较低(P<0.05)。与过表达组相比,沉默组p53、SAT1、ALOX15蛋白表达量较高(P<0.05)。结论沉默miR-572可能通过激活p53-SAT1-ALOX15信号通路,进而激活铁死亡,促进肾癌细胞凋亡、抑制索拉非尼耐药。Objective To explore the role of silencing microRNA-572(miR-572)in renal cell carcinoma cell apoptosis and sorafenib resistance through regulating ferroptosis.Methods The human renal cancer cell line 786-O was induced with blank control,or transfected with miR-572 siRNA,siRNA-NC,miR-572 overexpression plasmid and negative control plasmid using Lipofectamine 2000.Then,three sorafenib-resistant renal cell carcinoma cell lines were created.The expression of miR-572,apoptosis,sorafenib resistance and protein expressions of key proteins in the p53-SAT1-ALOX15 signaling pathway were observed.Results Compared with those transfected with miR-572 overexpression plasmid,miR-572 was significantly downregulated in 786-O cells transfected with miR-572 siRNA(P<0.05).Compared with those transfected with miR-572 overexpression plasmid,786-O cells transfected with miR-572 siRNA presented significantly higher apoptotic rate at 24h and 48h,lower half maximal inhibitory concentration(IC50)value and higher protein expressions of p53,SAT1 and ALOX15(P<0.05).Conclusion Silence of miR-572 promotes ferroptosis and apoptosis of renal cell carcinoma cells and inhibit sorafenib-resistance by activating the p53-SAT1-ALOX15 signaling pathway.

关 键 词：微小RNA-572 铁死亡 肾癌细胞 凋亡 索拉非尼耐药 

分 类 号：R692[医药卫生—泌尿科学]