Over-expression of long non-coding RNA NORAD promotes trophoblastic cell viability, migration, and invasion in preeclampsia via the miR-202-5p/FXR1 axis

Abstract

ObjectiveAbnormal expression of long non-coding RNAs (lncRNAs) is critical in preeclampsia (PE) pathogenesis. The current study explored the function of non-coding RNA activated by DNA damage (NORAD) in the progression of PE. Materials and methodsQuantitative real-time PCR was utilized to determine the expression of NORAD, microRNA (miR)-202-5p, and fragile X-related gene 1 (FXR1) in PE and normal placenta tissues. Cell viability was determined using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-h-tetrazolium bromide assay, and cell migration and invasion were assessed using the Transwell assay. Target relationships were confirmed with the dual-luciferase reporter assay. Western blotting was performed to determine the protein level of FXR1. ResultsNORAD expression was markedly reduced in PE placenta. NORAD over-expression enhanced the viability, migration, and invasion of HTR-8/SVneo cells. miR-202-5p was a target and was negatively regulated by NORAD. Down-regulation of miR-202-5p promoted the viability, migration, and invasion of HTR-8/SVneo cells. miR-202-5p inversely regulated FXR1 expression by targeting the 3′UTR of FXR1. Both miR-202-5p up-regulation and FXR1 knockdown reversed the NORAD over-expression-induced enhancement in the viability, migration, and invasion of HTR-8/SVneo cells. ConclusionCollectively, the results revealed that NORAD over-expression promoted trophoblast viability, invasion, and migration by regulating the miR-202-5p/FXR1 axis. These findings clarify PE pathogenesis and will inform the discovery of new targets for PE treatment.