从脐静脉内皮细胞中鉴定与子痫前期相关的mRNA、circRNA和lncRNA的ceRNA网络及潜在生物标志物
Identification of mRNA-, circRNA- and lncRNA- Associated ceRNA Networks and Potential Biomarkers for Preeclampsia From Umbilical Vein Endothelial Cells.
作者信息
Chen Dan, He Biwei, Zheng Panchan, Wang Shuying, Zhao Xueya, Liu Jinyu, Yang Xingyu, Cheng Weiwei
机构信息
International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Key Laboratory of Embryo Original Disease, Shanghai, China.
出版信息
Front Mol Biosci. 2021 Apr 20;8:652250. doi: 10.3389/fmolb.2021.652250. eCollection 2021.
OBJECTIVE
The etiology and pathogenesis of preeclampsia (PE) remain unclear, and ideal biomarkers for the early detection of PE are scarce. The involvement of the competing endogenous RNA (ceRNA) hypothesis in PE is only partially understood. The present study aimed to delineate a regulatory network in PE comprised of messenger RNAs (mRNAs), circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs) via ceRNA profiles from human umbilical vein endothelial cells (HUVECs) to further reveal the pathogenesis of PE and potential biomarkers.
METHODS
Differentially expressed mRNAs, circRNAs, and lncRNAs were detected in HUVECs from early onset preeclampsia (EOPE) cases ( = 4) and normal pregnancies ( = 4) by microarray analysis. Bioinformatics analysis was performed to systematically analyze the data, and a relevant ceRNA network was constructed. RNAs (, , , , , , , , , and ) were validated by quantitative real-time PCR (qRT-PCR) in 10 pairs of HUVECs and placental tissues from PE patients and normal pregnancies. Furthermore, expression of was detected in maternal peripheral blood samples from PE patients ( = 24) and normal pregnancies ( = 30) to confirm its potential as a novel biomarker. The receiver operating characteristic (ROC) curve was applied to analyze its diagnostic value.
RESULTS
Compared with HUVECs from normal pregnancies, HUVECs from EOPE cases had 33 differentially expressed mRNAs (DEmRNAs), 272 DEcircRNAs, and 207 DElncRNAs. GO and KEGG analyses of the DERNAs revealed the biological processes and pathways involved in PE. Based on the microarray data and the predicted miRNAs, a ceRNA network was constructed with four mRNAs, 34 circRNAs, nine lncRNAs, and 99 miRNAs. GO and KEGG analyses of the network reinforced the crucial roles of metabolic disorders, the p53 and JAK/STAT signaling pathways in PE. In addition, ROC analysis indicated that could be used as a novel biomarker for PE.
CONCLUSION
A novel ceRNA network was revealed in PE, and the potential of to serve as a new biomarker was confirmed.
目的
子痫前期（PE）的病因和发病机制仍不清楚，且用于早期检测PE的理想生物标志物稀缺。竞争性内源RNA（ceRNA）假说在PE中的作用仅得到部分理解。本研究旨在通过人脐静脉内皮细胞（HUVECs）的ceRNA谱描绘PE中由信使RNA（mRNAs）、环状RNA（circRNAs）、长链非编码RNA（lncRNAs）和微小RNA（miRNAs）组成的调控网络，以进一步揭示PE的发病机制和潜在生物标志物。
方法
通过微阵列分析在早发型子痫前期（EOPE）病例（n = 4）和正常妊娠（n = 4）的HUVECs中检测差异表达的mRNAs、circRNAs和lncRNAs。进行生物信息学分析以系统分析数据，并构建相关的ceRNA网络。通过定量实时PCR（qRT-PCR）在10对来自PE患者和正常妊娠的HUVECs及胎盘组织中验证RNA（，，，，，，，，，和）。此外，在PE患者（n = 24）和正常妊娠（n = 30）的母体外周血样本中检测的表达，以确认其作为新型生物标志物的潜力。应用受试者工作特征（ROC）曲线分析其诊断价值。
结果
与正常妊娠的HUVECs相比，EOPE病例的HUVECs有33个差异表达的mRNAs（DEmRNAs）、272个DEcircRNAs和207个DElncRNAs。对差异表达RNA（DERNAs）的基因本体（GO）和京都基因与基因组百科全书（KEGG）分析揭示了PE中涉及的生物学过程和途径。基于微阵列数据和预测的miRNAs，构建了一个由4个mRNAs、34个circRNAs、9个lncRNAs和99个miRNAs组成的ceRNA网络。对该网络的GO和KEGG分析强化了代谢紊乱、p53和JAK/STAT信号通路在PE中的关键作用。此外，ROC分析表明可作为PE的新型生物标志物。
结论
在PE中揭示了一个新的ceRNA网络，并证实了作为新生物标志物的潜力。
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