LncRNA H19通过调节miR-let7/MMP-9分子轴促进滋养细胞侵袭及迁移  

LncRNA H19 promotes trophoblast invasion and migration by regulating miR-let7/MMP-9 axis

作　　者：刘明嫦 刘师玚 马敬[1] Liu Mingchang;Liu Shiyang;Ma Jing(The First Affiliated Hospital of Kunming Medical University,Kunming 650031;Yunnan Maternal and Child Health Care Hospital,Kunming 650051)

机构地区：[1]昆明医科大学第一附属医院,昆明650031 [2]云南省妇幼保健院,昆明650051

出　　处：《现代妇产科进展》2023年第1期29-34,共6页Progress in Obstetrics and Gynecology

基　　金：云南省应用基础研究计划项目面上项目(No:2019FB095);云南省“万人计划”青年拔尖人才项目(No:YNWR-QNBJ-2018-169);国家自然科学基金资助项目(No:81460240)。

摘　　要：目的:通过检测妊娠期高血压疾病(HDP)患者胎盘组织中lncRNA H19、miR-let7、MMP-9表达,探索HDP发病机制。方法:收集2019年12月至2021年3月在昆明医科大学第一附属医院分娩的妊娠期高血压疾病(HDP)患者86例(PIH 26例,PE 29例,sPE 31例)和正常妊娠孕妇20例。分别对HTR-8/Svneo细胞进行敲减或过表达H19,过表达H19与miR-let7e-5p mimics共转染。RT-qPCR法检测胎盘组织及HTR-8/Svneo细胞中lncRNA H19、miR-let7、MMP-9 mRNA表达水平,免疫组化法检测胎盘组织中MMP-9蛋白表达水平。Transwell试验检测细胞侵袭力,细胞划痕实验检测细胞迁移力,CCK-8试验检测细胞活力。结果:与正常妊娠组相比,HDP患者胎盘组织中lncRNA H19表达明显上调,miR-let7b-5p、miR-let7e-5p及MMP-9蛋白表达均下调;PIH及sPE患者胎盘组织中MMP-9 mRNA表达下调。HTR/SVneo细胞中敲减H19后,lncRNA H19及MMP-9 mRNA表达减少,滋养细胞的侵袭力、迁移力及细胞活力均减弱,但miR-let7e-5p表达增多;过表达H19后的结果则相反。过表达H19与miR-let7e-5p mimics共转染后,HTR/SVneo细胞中miR-let7e-5p、MMP-9 mRNA表达增加情况以及滋养细胞的侵袭力、迁移力及细胞活力均被miR-let7e-5p逆转,但lncRNA H19表达量较单纯过表达H19时更高。结论:lncRNA H19通过抑制miR-let7e-5p表达,促进MMP-9 mRNA表达进而促进滋养细胞的侵袭、迁移力及细胞活力,参与HDP的发病机制。Objective:The expressions of lncRNA H19,miR-let7 and MMP-9 in the placenta of hypertensive disorders of pregnancy were detected to explore the pathogenesis of HDP.Methods:A total of 86 patients with hypertensive disorders of pregnancy(HDP)(26 PIH,29 cases PE,31 cases sPE)and 20 normal pregnant women were enrolled in the First Affiliated Hospital of Kunming Medical University from December 2019 to March 2021.We knocked down or overexpressed H19 in HTR-8/Svneo cells,or co-transfeeted H19-overexpressed plasmids with miR-let7e-5p mimics into HTR-8/Svneo cells.The expression levels of lncRNA H19,miR-let7e-5p and MMP-9 mRNA in placental tissues and HTR-8/Svneo cells were detected by RT-qPCR,and the protein expression levels of MMP-9 in placental tissues were detected by immunohistochemistry.Cell invasion was detected by Transwell assay,cell migration was detected by scratch assay,and cell viability was detected by CCK-8 assay.Results:Compared with the normal pregnancy group,the expression of lncRNA H19 in the placental tissues of HDP patients was significantly up-regulated,the expressions of miR-let7b-5p,miR-let7e-5p and MMP-9 protein were down-regulated,and the expression of MMP-9 mRNA in the placental tissues of PIH and sPE patients was down-regulated.After H19 knockdown in HTR/SVneo cells,the mRNA expressions of lncRNA H19 and MMP-9 were reduced,and the invasion,migration and cell viability of trophoblast cells were decreased,but the expression of miR-let7e-5p was increased,and the result was opposite after H19 overexpression.After co-transfection of overexpressed H19 with miR-let7e-5p mimics,the increased expression of miR-let7e-5p and MMP-9 mRNA in HTR/SVneo cells,as well as the invasion,migration and cell viability of trophoblast cells were reversed by miR-let7e-5p.However,the expression level of lncRNA H19 was higher than that of H19 overexpression alone.Conclusions:lncRNA H19 is involved in the pathogenesis of HDP by inhibiting the expression of miR-let7e-5p and promoting the expression of MMP-9 mRNA,thus promo

关 键 词：H19 miR-let7 MMP-9 滋养细胞 妊娠期高血压疾病 

分 类 号：R714.7[医药卫生—妇产科学]