河北医药2024,Vol.46Issue(5) :693-696.DOI:10.3969/j.issn.1002-7386.2024.05.010

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

潘亮 畅雅学 段万里 邓骞
河北医药2024,Vol.46Issue(5) :693-696.DOI:10.3969/j.issn.1002-7386.2024.05.010

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

潘亮 1畅雅学 1段万里 1邓骞1
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作者信息

  • 1. 710061 西安市,陕西省人民医院泌尿外科
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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.

Abstract

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

Key words

microrna-572/ferroptosis/renal cell carcinoma cells/apoptosis/sorafenib resistance

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基金项目

陕西省自然科学基础研究计划(2021JQ-910)

出版年

2024
河北医药
河北省医学情报研究所

河北医药

CSTPCD
影响因子:1.075
ISSN:1002-7386
参考文献量21
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