子痫前期胎盘组织miRNA差异表达谱生物学分析及miR-365a-3p参与发病的机制探讨  

Biological analysis of miRNA differential expression profile in placenta of preeclampsia and the mechanism of miR-365a-3p in the pathogenesis of preeclampsia

作　　者：李晖[1] 焦顺 郑晓丹 肖黎[1] 陈智芳 刘荣 LI Hui;JIAO Shun;ZHENG Xiaodan;XIAO Li;CHEN Zhifang;LIU Rong(Jingzhou Central Hospital,Jingzhou 434020,China)

机构地区：[1]荆州市中心医院,湖北荆州434020

出　　处：《山东医药》2020年第11期29-33,共5页Shandong Medical Journal

基　　金：湖北省荆州市科技局科研基金资助项目(2017035)。

摘　　要：目的建立子痫前期胎盘组织miRNA差异表达谱并对其生物学功能进行分析,探讨差异表达谱中变化最显著的miR-365a-3p参与子痫前期发病的相关机制。方法采用高通量测序技术对子痫前期和正常胎盘组织(各3例份)进行miRNA表达谱测序,DeSeq2分析差异表达,对差异表达miRNA的靶基因进行GO及KEGG功能富集分析。可视化软件StarBase 3.0显示miR-365a-3p(差异表达谱中表达上调最显著的miRNA)与TGF-β通路关键基因SMAD2、MAPK1的3′非编码区均存在靶向结合位点。采用real-time PCR法检测子痫前期和正常胎盘组织(各41例份)miR-365a-3p及SMAD2、MAPK1 mRNA表达,并分析其相关性。结果与正常胎盘组织相比,子痫前期胎盘组织中有44个miRNA差异表达,其中12个miRNA表达显著上调、32个miRNA表达显著下调。GO及KEGG富集分析结果显示,差异表达miRNA潜在靶基因主要参与子宫内膜癌、TGF-β信号通路、Wnt信号通路、急性粒细胞白血病、mTOR信号通路、醛固酮调节钠的重吸收、慢性粒细胞白血病、胰岛素信号通路、ErbB信号通路、癌症发生等。子痫前期胎盘组织miR-365a-3p相对表达量高于正常胎盘组织,SMAD2、MAPK1 mRNA相对表达量均低于正常胎盘组织(P均<0.01)。子痫前期胎盘组织中miR-365a-3p与SMAD2、MAPK1 mRNA表达均呈显著负相关关系(P均<0.05)。结论子痫前期胎盘组织存在异常表达的miRNA,并参与诸多信号通路;子痫前期胎盘组织miR-365a-3p表达升高,其可能通过负性调控TGF-β信号通路参与子痫前期的发病。Objective To explore the biological function of miRNA differential expression profile in placenta of preeclampsia,and to explore the mechanism of miR-365a-3p,which is the most significant differentially expressed miRNA,in the pathogenesis of preeclampsia.Methods High-throughput sequencing technology was used to sequence the miRNA expression profile of preeclampsia placental tissues and normal placental tissues(with 3 cases in each).DeSeq2 was conducted to analyze differentially expressed miRNAs,and GO and KEGG function enrichment analysis was performed on target genes predicted by differentially expressed miRNAs.Visualization software StarBase 3.0 revealed that there were targeted binding sites between miR-365a-3p and 3'-UTRs of SMAD2 and MAPK1(the key genes of TGF-βpathway).Real-time PCR was used to detect miR-365a-3p,SMAD2 and MAPK1 mRNA expression in preeclampsia and normal placental tissues(with 41 cases in each),and the correlations was analyzed.Results Compared with the normal placental tissues,there were 44 miRNAs differentially expressed in preeclampsia placenta,among which 12 miRNAs were significantly up-regulated and 32 miRNAs were significantly down-regulated.GO and KEGG enrichment analysis results showed that the potential target genes of the differentially expressed miRNAs were mainly involved in endometrial cancer,TGF-βsignaling pathway,Wnt signaling pathway,acute myeloid leukemia,mTOR signaling pathway,aldosterone-regulated sodium reabsorption,chronic granulocytes cell leukemia,insulin signaling pathway,ErbB signaling pathway,and cancer development.The relative expression of miR-365a-3p in the preeclampsia placenta was higher than that of normal placenta,and the relative expression of SMAD2 and MAPK1 mRNA was lower than that of normal placenta(all P<0.01).There was a significant negative correlation between miR-365a-3p and SMAD2 and MAPK1 mRNA expression in preeclampsia placenta(both P<0.05).Conclusion There is abnormal expression of miRNAs in preeclampsia placenta,which is involved in many signa

关 键 词：子痫前期 微小RNA 差异表达谱 miR-365a-3p TGF-β通路 

分 类 号：R714.25[医药卫生—妇产科学]