Roles of miR-1246, miR-146, and miR-155 and Their Targets in Human Trophoblast Differentiation

The 54th Annual Medical Student Research Forum at UT Southwestern Medical Center (Monday, January 19, 2016, 2-5 p.m., D1.700) ; Each year the Medical Student Research Program awards students for the best oral presentation and the best poster presentation as judged by faculty across campus. This author received an award as one of the best poster presentations at this forum. ; BACKGROUND: Abnormal placental implantation has been implicated in preeclampsia (PE), a devastating hypertensive disorder of pregnancy that is a leading cause of maternal and neonatal morbidity and mortality. Placental development depends upon fetal cytotrophoblast (CytT) invasion into the maternal decidua and enlargement of the uterine arterioles with increased blood flow and O2 availability to chorionic villi. CytT fuse and differentiate into syncytiotrophoblast (SynT), which mediate gas and nutrient exchange between mother and fetus, and produce several key steroid and polypeptide hormones of pregnancy. Recent studies from our lab suggest that SynT differentiation is regulated by differentially expressed microRNAs (miRNA/miR). By miRNA microarray of RNA from mid-gestation human CyT before and after differentiation to SynT in culture, miR-1246, miR-146, and miR-155 were found to be highly and significantly upregulated. Interestingly, miR-1246 and miR-155 have been predicted and proven, respectively, to target Jarid2, which recruits the polycomb repressive complex (PRC) 2 to developmentally-regulated genes. PRC2 catalyzes methylation of histone H3 on lysine 27. This chromatin mark promotes recruitment of the PRC1 complex, resulting in repressed chromatin. Moreover, miR-1246, miR-155 and miR-146 all are predicted to modulate components of the Wnt signaling pathway, which plays an integral role in placental development. OBJECTIVE: To analyze expression of miR-155, miR-1246, miR-146 and their targets during differentiation of human trophoblasts in culture and effects of hypoxia. METHODS: CytT were isolated from mid-gestation human placenta and ...