Development and Validation of a Four Micro RNA-Mediated Signature for Placenta Accreta: An Integrated Competing Endogenous RNA Network Analysis

Abstract

Background: In this study, we examined the regulatory network comprising long non-coding (lnc), micro (mi), and messenger (m) RNAs in the placenta accreta spectrum (PAS) to elucidate its underlying mechanisms and identify biomarkers for the prediction of intraoperative blood volume loss. Methods: Using RNA sequencing, we compared mRNA, lncRNA, and miRNA expression profiles between five placenta accreta and five normal tissues and the miRNA expression profiles in ten maternal plasma samples from placenta accreta and control participants. Findings: Upon comparing PAS and control placentas, we identified 8806 lncRNAs, 128 miRNAs, and 1788 mRNAs that were differentially expressed. On the basis of predictions of the relationships between lncRNA and miRNA and miRNA and mRNA, we developed a competing endogenous (ce) RNA network comprising 20 lncRNAs, 4 miRNAs, and 19 mRNAs. This network implicated a reduced angiogenesis pathway, and, based on correlation analysis, we propose that two miRNAs (hsa-miR‐490-3p and hsa-miR-133a-3p) could serve as biomarkers of PAS prognosis. Interpretation: On the basis of ceRNA network analysis, we identified lncRNAs, miRNAs, and mRNAs that clarify the pathogenesis of PAS, some of which may have potential utility as biomarkers of PAS prognosis. Funding Statement: The study was supported by the project of “The National Key Research and Development Program of Reproductive Health & Major Birth Defects Control and Prevention” (No. 2016YFC100404 to Chong Qiao) and the Science and Technology Project of Liaoning Provincial Education Department (No. LS201611 to Na Li). Declaration of Interests: The authors declare that there is no conflict of interest. Ethics Approval Statement: The study was approved by the Shengjing Hospital and China Medical University. All participants enrolled in this study provided written informed consent.