Objective: Abnormal 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 methods: Quantitative 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.
Results: NORAD 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.
Conclusion: Collectively, 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.
Keywords: Fragile X-related gene 1; MiR-202-5p; NORAD; Preeclampsia; Trophoblast.
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