MiR-214-5p suppresses the proliferation, migration and invasion of trophoblast cells in pre-eclampsia by targeting jagged 1 to inhibit notch signaling pathway

Abstract

MicroRNA-214-5p has been reported to be expressed in placental tissue and suppressed the proliferation and invasion of various tumor cells. However, the role of miR-214-5p in pre-eclampsia has not been reported. We aimed to explore the effects of miR-214-5p in proliferation, migration, and invasion of placental trophoblast cells. RT-qPCR was used to quantify the miR-214-5p expression level in placental samples and four types of trophoblast cell lines. Cell proliferation was monitored by CCK-8 and Edu staining assays. Flow cytometry was used to determine the cell cycle. Wound healing and transwell assays were performed to measure the migratory and invasive capacities in JEG-3 and BEWO cells. In addition, we investigated whether miR-214-5p targeted Jagged 1 to regulate the Notch signaling pathway to affect trophoblast cells by luciferase assay and western blot. The expression of miR-214-5p was significantly increased in the placenta of patients with PE. Moreover, the proliferation, migration, and invasion of JEG-3 cells transfected with miR-214-5p mimic were inhibited. The results were reversed when BEWO cells were transfected with miR-214-5p inhibitor. The dual-luciferase assay demonstrated that miR-214-5p directly regulated Jagged 1. The expression of the proteins associated with the Notch signaling pathway, Jagged 1, Notch 1, HEY 1 and HES 1 were all decreased when Jagged 1 was negatively regulated by miR-214-5p. miR-214-5p directly down-regulated Jagged 1 expression, then suppressed proliferation, migration, and invasion of human placental trophoblast cells by inhibiting the Notch signaling pathway.