Identification of Urothelial Cancer-Associated 1 (UCA1) as a diagnostic biomarker of pre-eclampsia via regulating microRNA-16 and its downstream signaling pathway

Abstract

IntroductionIn this study, we studied the clinical value of using urothelial cancer-associated 1 (UCA1) and microRNA-16 (miR-16) as biomarkers for the diagnosis of pre-eclampsia (PE). Also, we compared the diagnostic values of miR-16, UCA1 and pregnancy-associated plasma protein-A (PAPP-A) in PE. Furthermore, we investigated the interaction between miR-16 and UCA1/PAPP-A.Material and methods128 PE patients and 172 healthy pregnant women were enrolled in this study. Receiver operating characteristic (ROC) analysis was carried out to predict the diagnostic values of UCA1, miR-16 and PAPP-A in PE. Enzyme-linked immunosorbent assay (ELISA), real-time polymerase chain reaction (PCR), Western blot analysis, immunohistochemistry (IHC) assay, computational analysis, and luciferase assay were conducted to measure the differential expression of UCA1, miR-16, and PAPP-A while establishing a signaling pathway of UCA1/miR-16/PAPP-A.ResultsCompared with miR-16 and PAPP-A, UCA1 exhibited a better value in the diagnosis of PE. The expression of PAPP-A and UCA1 was down-regulated while the expression of miR-16 was up-regulated in patients with PE, especially in patients with HELLP pregnancies. Moreover, UCA1 was identified as a sponge of miR-16, while PAPP-A mRNA was identified as a virtual target gene of miR-16. Finally, a negative regulatory relationship was observed between the expression of miR-16 and UCA1 or PAPP-A, while the expression of UCA1 and PAPP-A were positively related.ConclusionsTaken together, UCA1 could be used as a more valuable biomarker in the diagnosis of PE. Meanwhile, the reduced expression of UCA1 could exert a positive effect by reducing the expression of PAPP-A in the pathogenesis of PE.