학술논문
Discovery and Verification of Extracellular miRNA Biomarkers for Non-invasive Prediction of Pre-eclampsia in Asymptomatic Women
Document Type
article
Author
Srinivasan, Srimeenakshi; Treacy, Ryan; Herrero, Tiffany; Olsen, Richelle; Leonardo, Trevor R; Zhang, Xuan; DeHoff, Peter; To, Cuong; Poling, Lara G; Fernando, Aileen; Leon-Garcia, Sandra; Knepper, Katharine; Tran, Vy; Meads, Morgan; Tasarz, Jennifer; Vuppala, Aishwarya; Park, Soojin; Laurent, Clara D; Bui, Tony; Cheah, Pike See; Overcash, Rachael Tabitha; Ramos, Gladys A; Roeder, Hilary; Ghiran, Ionita; Parast, Mana; Consortium, The PAPR Study; Boggess, Kim A; Saade, George R; Sullivan, Scott A; Markenson, Glenn R; Iams, Jay D; Coonrod, Dean V; Pereira, Leonardo M; Esplin, M Sean; Cousins, Larry M; Lam, Garrett K; Hoffman, Matthew K; Breakefield, Xandra O; Lueth, Amir J; Rust, Sharon R; Dufford, Max T; Fox, Angela C; Hickok, Durlin E; Burchard, Julja; Boniface, J Jay; Laurent, Louise C
Source
Cell Reports Medicine. 1(2)
Subject
Language
Abstract
Development of effective prevention and treatment strategies for pre-eclampsia is limited by the lack of accurate methods for identification of at-risk pregnancies. We performed small RNA sequencing (RNA-seq) of maternal serum extracellular RNAs (exRNAs) to discover and verify microRNAs (miRNAs) differentially expressed in patients who later developed pre-eclampsia. Sera collected from 73 pre-eclampsia cases and 139 controls between 17 and 28 weeks gestational age (GA), divided into separate discovery and verification cohorts, are analyzed by small RNA-seq. Discovery and verification of univariate and bivariate miRNA biomarkers reveal that bivariate biomarkers verify at a markedly higher rate than univariate biomarkers. The majority of verified biomarkers contain miR-155-5p, which has been reported to mediate the pre-eclampsia-associated repression of endothelial nitric oxide synthase (eNOS) by tumor necrosis factor alpha (TNF-α). Deconvolution analysis reveals that several verified miRNA biomarkers come from the placenta and are likely carried by placenta-specific extracellular vesicles.