Potential pathophysiological role of microRNA 193b-5p in human placentae from pregnancies complicated by preeclampsia an
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ORIGINAL ARTICLE
Potential pathophysiological role of microRNA 193b‑5p in human placentae from pregnancies complicated by preeclampsia and intrauterine growth restriction Zain Awamleh1,2 · Victor K. M. Han1,2,3 Received: 6 January 2020 / Accepted: 2 August 2020 © Springer Nature B.V. 2020
Abstract Preeclampsia (PE) and intrauterine growth restriction (IUGR) are pregnancy complications resulting from abnormal placental development. MicroRNAs can regulate placental development and contribute to disease, by influencing gene expression. Our previous study revealed an increase in miR-193b-5p expression in placentae from patients with early-onset pregnancy complications and identified candidate gene targets for miR-193b-5p. The purpose of this study is two-fold, first to validate candidate gene targets predicted for miR-193b-5p from microRNA-RNA expression data. Second, to overexpress miR193b-5p in a trophoblast cell line (HTR-8/SVneo) to assess impact on trophoblast cell proliferation and migration. Integration of the miRNA and RNA sequencing expression data revealed 10 candidate gene targets for miR-193b-5p across all patient groups (PE only, IUGR only, PE + IUGR). Luciferase experiments identified two gene targets for miR-193b-5p, APLN and FGF13. Real-time PCR confirmed a median 45% decrease of FGF13 expression across 3 patient groups, and 50% decrease of APLN expression in patients with PE + IUGR. Following transfection of HTR-8/SVneo cells with miR-193b-5p mimics, APLN and FGF13 mRNA expression in HTR-8/SVneo was reduced by a median percentage of 30% and 45%, respectively. Concomitantly, HTR-8/SVneo cells demonstrate 40% reduction in cell migration. APLN and FGF13 immunoreactivity was identified strongly in the cytotrophoblast cells of the human placentae. These findings suggest that miR-193b-5p may contribute to trophoblast dysfunction observed in pregnancy complications such as PE and IUGR. Keyword microRNA-193b · Placenta · Trophoblast · Preeclampsia · Intrauterine growth restriction Abbreviations APLN Apelin CT Cytotrophoblast EO Early-onset EVT Extravillous trophoblast Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11033-020-05705-y) contains supplementary material, which is available to authorized users. * Zain Awamleh [email protected] 1
Children’s Health Research Institute, 800 Commissioners Road East, London, ON N6C 2V5, Canada
2
Department of Biochemistry, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON N6A 3K7, Canada
3
Department of Pediatrics, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON N6A 3K7, Canada
FGF13 Fibroblast growth factor 13 GO Gene ontology IHC Immunohistochemistry IUGR Intrauterine growth restriction miRNA MicroRNA NGS Next generation sequencing PE Preeclampsia qRT-PCR Quantitative real time PCR SCT Syncytiotrophoblast
Introduction Micro(mi)RNAs are endogenous, single stranded noncoding RNAs that regulate gene expression post-
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