Abstract
BackgroundThe etiology and pathogenesis of pre-eclampsia (PE) is unclear, and there is no ideal early clinical biomarker for prediction of PE. The competing endogenous RNA (ceRNA) hypothesis is a new approach to uncover the molecular pathology of PE. The first aim of this study was to perform messenger RNA, long non-coding RNA, and circular RNA (circRNA) expression profiling of human normal and severe pre-eclampsia (SPE) placentas. circRNA, which has a stable structure, is a more suitable biomarker than other types of RNA. Therefore, the second aim of our study was to select some differentially expressed circRNAs in PE placentas as early clinical biomarkers of PE in blood circulation.ResultsUsing microarray analysis, we investigated differentially expressed ceRNAs in human normal and SPE placentas. Bioinformatics, such as gene ontology, KEGG pathway, and ceRNA network analyses, were performed to evaluate the microarray data and gain further insights into the biological processes. RNAs (Chd5, Furin, lnc-ELAVL4-9:1, lnc-RAP1GAP2-5:2, hsa_circ_0036877, hsa_circ_0036878, hsa_circ_0055724, hsa_circ_0049730, and hsa_circ_0036474) were validated by quantitative real-time PCR (qRT-PCR). RNA immunoprecipitation (RIP) of AGO2 in htra-8 cells and qRT-PCR analysis of hsa_circ_0036877 expression in maternal whole peripheral blood samples of participants were then conducted to confirm that hsa_circ_0036877 is a ceRNA and potential novel blood biomarker for early PE, respectively.ConclusionOur study is the first systematic profiling of ceRNAs in placentas of PE patients and revealed the global ceRNA network integration in PE. Moreover, hsa_circ_0036877 can function as a ceRNA and serve as a potential novel blood biomarker for early PE.
Highlights
The etiology and pathogenesis of pre-eclampsia (PE) is unclear, and there is no ideal early clinical biomarker for prediction of PE
Our study focused on competing endogenous RNA (ceRNA), which may facilitate uncovering the etiology and pathogenesis of PE
After applying a stringent filtering approach that compared severe pre-eclampsia (SPE) and N groups, we identified 731 upregulated and 1617 downregulated messenger RNA (mRNA), 5127 upregulated and 3813 downregulated Long non-coding RNA (lncRNA), and 4569 upregulated and 3984 downregulated circular RNA (circRNA)
Summary
The etiology and pathogenesis of pre-eclampsia (PE) is unclear, and there is no ideal early clinical biomarker for prediction of PE. The first aim of this study was to perform messenger RNA, long non-coding RNA, and circular RNA (circRNA) expression profiling of human normal and severe pre-eclampsia (SPE) placentas. The second aim of our study was to select some differentially expressed circRNAs in PE placentas as early clinical biomarkers of PE in blood circulation. Long non-coding RNA (lncRNA) and circular RNA (circRNA) can share microRNA (miRNA) response elements of linear messenger RNA (mRNA), which competitively bind to miRNAs, affecting the regulatory function of miRNAs and gene. The competing endogenous RNA (ceRNA) hypothesis suggests an interaction network between miRNAs, lncRNAs, circRNAs, and mRNAs. circRNAs can function as a ceRNA to regulate gene expression. Our study focused on ceRNAs, which may facilitate uncovering the etiology and pathogenesis of PE
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