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Abstract
Background Preeclampsia (PE) is a pregnancy-specific hypertension syndrome and is one of the leading causes of maternal and perinatal morbidity and mortality. Long noncoding RNAs (lncRNAs) have been reported to be abnormally expressed in many diseases, including preeclampsia. The present study is aimed at identifying the key genes and lncRNA-associated competing endogenous RNA (ceRNA) networks in early-onset preeclampsia (EOPE). Methods We investigated expression profiles of differentially expressed lncRNAs (DElncRNAs) and genes (DEGs) in placental tissues of EOPE and healthy controls with Human LncRNA Array v4. The potential functions of DEGs and DElncRNAs were predicted using the clusterProfiler package. The lncRNA-mRNA coexpression network was constructed via Pearson's correlation coefficient. The protein-protein interaction (PPI) network of DEGs was constructed, and the hub genes were obtained using the STRING database and Cytoscape. The ceRNA networks were constructed based on miRWalk and LncBase v2. qRT-PCR was performed to confirm the expression of lncRNA MIR193BHG, PROX1-AS1, and GATA3-AS1. ROC curves were performed to assess the clinical value of lncRNA MIR193BHG, PROX1-AS1, and GATA3-AS1 in the diagnosis of EOPE. Results We found 6 hub genes (SPP1, CCR2, KIT, ENG, ACKR1, and FLT1) altered in placental tissues of EOPE and constructed a ceRNA network, including 21 lncRNAs, 3 mRNAs, and 69 miRNAs. The expression of lncRNA MIR193BHG and GATA3-AS1 were elevated and showed good clinical values for diagnosing EOPE. Conclusion This study provides novel insights into the lncRNA-related ceRNA network in EOPE and identified two lncRNAs as potential prognostic biomarkers in EOPE.
Highlights
Preeclampsia (PE) is a pregnancy-specific complication associated with new-onset hypertension, affecting an estimated 4-5% of pregnancies worldwide [1]
We identified 246 DElncRNAs, including 159 upregulated Long noncoding RNAs (lncRNAs) and 87 downregulated lncRNAs (Figure 1(c)), and 224 DEGs, including 167 upregulated mRNAs and 57 downregulated mRNAs (Figure 1(d))
A total of 91 DEGs were mapped into this network (Figure 4(a)). We evaluated their degree of connection and identified 6 hub genes including secreted phosphoprotein 1 (SPP1), C-C chemokine receptor type 2 (CCR2), receptor tyrosine kinase (KIT), endoglin (ENG), atypical chemokine receptor 1 (ACKR1), and fms related tyrosine kinase 1 (FLT1)
Summary
Preeclampsia (PE) is a pregnancy-specific complication associated with new-onset hypertension, affecting an estimated 4-5% of pregnancies worldwide [1]. It often presents with proteinuria or other end-organ damages in the mother after 20 weeks of gestation [2]. The present study is aimed at identifying the key genes and lncRNA-associated competing endogenous RNA (ceRNA) networks in early-onset preeclampsia (EOPE). We found 6 hub genes (SPP1, CCR2, KIT, ENG, ACKR1, and FLT1) altered in placental tissues of EOPE and constructed a ceRNA network, including 21 lncRNAs, 3 mRNAs, and 69 miRNAs. The expression of lncRNA MIR193BHG and GATA3-AS1 were elevated and showed good clinical values for diagnosing EOPE.
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