Identification of mRNA-, circRNA- and lncRNA- Associated ceRNA Networks and Potential Biomarkers for Preeclampsia From Umbilical Vein Endothelial Cells.
Identification of mRNA-, circRNA- and lncRNA- Associated ceRNA Networks and Potential Biomarkers for Preeclampsia From Umbilical Vein Endothelial Cells.
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DOI：
10.3389/fmolb.2021.652250
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发表时间：
2021
影响因子：
5
通讯作者：
Cheng W
中科院分区：
文献类型：
--
作者：
Chen D;He B;Zheng P;Wang S;Zhao X;Liu J;Yang X;Cheng W
先兆子痫（PE）的病因和发病机制仍不清楚，并且早期检测PE的理想生物标志物也很少。竞争性内源性 RNA (ceRNA) 假说在 PE 中的作用目前尚不完全清楚。本研究旨在通过人脐静脉内皮细胞（HUVEC）的ceRNA图谱描绘PE中由信使RNA（mRNA）、环状RNA（circRNA）、长链非编码RNA（lncRNA）和微小RNA（miRNA）组成的调控网络，以进一步揭示PE的发病机制和潜在的生物标志物。通过微阵列分析，在早发先兆子痫 (EOPE) 病例 (n = 4) 和正常妊娠 (n = 4) 的 HUVEC 中检测到差异表达的 mRNA、circRNA 和 lncRNA。通过生物信息学分析对数据进行系统分析，并构建相关的ceRNA网络。 RNA（ANGPT2、LIPG、hsa_circ_0025992、hsa_circ_0090396、hsa_circ_0066955、hsa_circ_0041203、hsa_circ_0018116、lnc-C17orf64-1:1、lnc-SLC27A2-2:1 和 lnc-UEVLD-5:1）通过实时定量 PCR (qRT-PCR) 对来自 PE 患者和正常妊娠的 10 对 HUVEC 和胎盘组织进行了验证。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到 hsa_circ_0025992 的表达，以证实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。与正常妊娠的HUVEC相比，EOPE病例的HUVEC有33个差异表达的mRNA（DEmRNA）、272个DEcircRNA和207个DElncRNA。 DERNA 的 GO 和 KEGG 分析揭示了 PE 涉及的生物过程和途径。基于微阵列数据和预测的 miRNA，由 4 个 mRNA、34 个 circRNA、9 个 lncRNA 和 99 个 miRNA 构建了 ceRNA 网络。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 hsa_circ_0025992 可用作 PE 的新型生物标志物。 PE 中揭示了一种新的 ceRNA 网络，并证实了 hsa_circ_0025992 作为新生物标志物的潜力。
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. Differentially expressed mRNAs, circRNAs, and lncRNAs were detected in HUVECs from early onset preeclampsia (EOPE) cases (n = 4) and normal pregnancies (n = 4) by microarray analysis. Bioinformatics analysis was performed to systematically analyze the data, and a relevant ceRNA network was constructed. RNAs (ANGPT2, LIPG, hsa_circ_0025992, hsa_circ_0090396, hsa_circ_0066955, hsa_circ_0041203, hsa_circ_0018116, lnc-C17orf64-1:1, lnc-SLC27A2-2:1, and lnc-UEVLD-5:1) 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 hsa_circ_0025992 was detected in maternal peripheral blood samples from PE patients (n = 24) and normal pregnancies (n = 30) to confirm its potential as a novel biomarker. The receiver operating characteristic (ROC) curve was applied to analyze its diagnostic value. 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 hsa_circ_0025992 could be used as a novel biomarker for PE. A novel ceRNA network was revealed in PE, and the potential of hsa_circ_0025992 to serve as a new biomarker was confirmed.
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作者：
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通讯作者：
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