期刊
MOLECULAR BIOLOGY REPORTS
卷 47, 期 9, 页码 6531-6544出版社
SPRINGER
DOI: 10.1007/s11033-020-05705-y
关键词
microRNA-193b; Placenta; Trophoblast; Preeclampsia; Intrauterine growth restriction
资金
- Canadian Institutes of Health Research [15579, 15262]
- Douglas and Vivian Bocking Chair in Fetal and Newborn Growth
- Western University
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 miR-193b-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,APLNandFGF13. Real-time PCR confirmed a median 45% decrease ofFGF13expression across 3 patient groups, and 50% decrease ofAPLNexpression in patients with PE + IUGR. Following transfection of HTR-8/SVneo cells with miR-193b-5p mimics,APLNandFGF13mRNA 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.
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