Development and validation of a four-microRNA signature for placenta accreta spectrum: an integrated competing endogenous RNA network analysis

Background: Placenta accreta spectrum (PAS) is a major cause of maternal morbidity and mortality in modern obstetrics, however, few studies have explored the underlying molecular mechanisms and biomarkers. In this study, we aimed to elucidate the regulatory RNA network contributing to PAS, comprising long non-coding (lnc), micro (mi), and messenger (m) RNAs, 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 PAS and five normal placental tissues. Furthermore, the miRNA expression profiles in maternal plasma samples from ten PAS and ten control participants were assessed. The data and clinical information were analyzed using R language and GraphPad Prism 7 software. Results: Upon comparing PAS and control placentas, we identified 8,806 lncRNAs, 128 miRNAs, and 1,788 mRNAs that were differentially expressed. Based on a lasso regression analysis and correlation predictions, we developed a competing endogenous (ce) RNA network comprising 20 lncRNAs, 4 miRNAs, and 19 mRNAs. This network implicated a reduced angiogenesis pathway in PAS, and correlation analyses indicated that two mi RNAs (hsa-mi R-490-3p and hsa-mi R-133a-3p) were positively correlated to operation-related blood volume loss. Conclusions: We identified a ceRNA regulatory mechanism in PAS, and two miRNAs that may potentially serve as biomarkers of PAS prognosis.