首页|miR-519e-5p/SAT1轴介导铁死亡信号通路调节子宫内膜异位症的发生发展

miR-519e-5p/SAT1轴介导铁死亡信号通路调节子宫内膜异位症的发生发展

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目的 探讨微小RNA-519e-5p(miR-519e-5p)靶向调节精胺N1-乙酰基转移酶1(SAT1)对子宫内膜异位症(EMS)的影响.方法 收集2023年1-6月在上海健康医学院附属周浦医院住院治疗的卵巢子宫内膜异位症患者的异位内膜组织,检测miR-519e-5p、SAT1蛋白表达;从异位病变组织分离细胞,将细胞分为Contro l组、anti-miR-NC组、anti-miR-519e-5p 组、anti-miR-519e-5p+NC 组、anti-miR-519e-5p+sh-SAT 1 组,分别检测萤光素酶活性、细胞活性、活细胞数和死细胞数、Fe2+、ROS、GSH和MDA;普鲁士蓝染色观察铁颗粒分布情况;RT-qPCR检测miR-519e-5p、SAT1 mRNA表达;Western blot检测SAT1、GPX4、SLC7A11、MUC1、ACSL4蛋白表达.结果 与正常子宫内膜组织比较,子宫内膜异位症患者异位内膜组织中miR-519e-5p显著增加,SAT1表达显著降低(P<0.05);萤光素酶报告基因检测结果显示,miR-519e-5p与SAT1存在靶向关系;抑制miR-519e-5p后,细胞活性、GSH、GPX4、SLC7A11、MUC1显著降低,Fe平均光密度值、Fe2+、MDA、ROS、ACSL4显著增加(P<0.05);沉默SAT1并抑制miR-519e-5p表达,细胞活性、GSH、GPX4、SLC7A11、MUC1显著增加,Fe平均光密度值、Fe2+、MDA、ROS、ACSL4显著降低(P<0.05).结论 miR-519e-5p在子宫内膜异位症中上调表达,抑制miR-519e-5p表达可激活铁死亡信号通路,抑制子宫内膜异位症的发生.
MiR-519e-5p/SAT1 axis regulates the occurrence and development of endometriosis by mediating ferroptosis signal pathway
Objective To investigate the effect of microRNA-519e-5p(miR-519e-5p)on endometriosis by targeting the regulation of spermine N1-acetyltransferase 1(SAT1).Methods From January 2023 to June 2023,the ectopic endo-metrium tissues of patients with ovarian endometriosis hospitalized in Zhoupu Hospital Affiliated to Shanghai University of Medicine & Health Sciences were collected,and the expression of miR-519e-5p and SAT1 proteins was detected;cells were isolated from ectopic lesion tissue and separated into Control group,anti-miR-NC group,anti-miR-519e-5p group,anti-miR-519e-5p+NC group,and anti-miR-519e-5p+sh-SATl group,luciferase activity,cell activity,numbers of live and dead cells,Fe2+,ROS,GSH,and MDA were detected separately.Prussian blue staining was applied to observe the distribution of iron particles.RT-qPCR was applied to detect miR-519e-5p and SAT1 mRNA expression;and Western blot was applied to detect the expression of SAT1,GPX4,SLC7A11,MUC1,and ACSL4 proteins.Results Compared with normal endometrium,miR-519e-5p obviously increased and SAT1 expression obviously decreased in ectopic endometrial tissue(P<0.05).The de-tection results of luciferase reporter gene showed that miR-519e-5p had a targeting relationship with SAT1.After inhibiting miR-519e-5p,cell activity,GSH,GPX4,SLC7A11,MUC1 were obviously reduced,while the average optical density of Fe,Fe2+,MDA,ROS,and ACSL4 were obviously increased(P<0.05).Silencing SAT1 and inhibiting miR-519e-5p expression obviously increased cell activity,GSH,GPX4,SLC7A11,and MUC1,and obviously decreased the average optical density of Fe,Fe2+,MDA,ROS,and ACSL4(P<0.05).Conclusion The expression of miR-519e-5p is up-regulated in endometriosis.Inhibiting the expression of miR-519e-5p was able to activate the ferroptosis signal pathway and inhibit the occurrence of endometriosis.

microRNA-519e-5pspermine N1-acetyltransferase 1ferroptosisendometriosiscell activity

王鹰、吴建发、胡晓英、姜伶俐、柳洲

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上海健康医学院附属周浦医院妇产科,上海 201318

微小RNA-519e-5p 精胺N1-乙酰基转移酶1 铁死亡 子宫内膜异位症 细胞活性

上海市浦东新区卫生系统重点学科群建设项目

PWZxq2022-15

2024

中国优生与遗传杂志
中国优生科学协会

中国优生与遗传杂志

CSTPCD
影响因子:0.527
ISSN:1006-9534
年,卷(期):2024.32(4)