Circ_0001326 suppresses trophoblast cell proliferation, invasion, migration and epithelial-mesenchymal transition progression in preeclampsia by miR-188-3p/HtrA serine peptidase 1 axis

Background: It has been reported that the alteration of circular RNAs (circRNAs) during preeclampsia (PE) can be associated with the pathogenesis of this disease. Herein, this work investigated the potential functions and mechanism of circ_0001326 in PE process.

Methods: The levels of genes and proteins were evaluated by quantitative real-time PCR (qRT-PCR) and western blotting. The functional experiments were conducted using cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, and wound healing assays, respectively. The binding between miR-188-3p and circ_0001326 or HtrA serine peptidase 1 (HTRA1) was verified by bioinformatics analysis and dual-luciferase reporter assays.

Results: Circ_0001326 and HTRA1 expression was increased, while miR-188-3p expression was decreased in the placental tissues of preeclamptic singleton pregnant women compared with the normal pregnant women. Functionally, up-regulation of circ_0001326 or HTRA1, or down-regulation of miR-188-3p led to the arrest of cell growth, invasion, migration and epithelial-mesenchymal transition (EMT) process in trophoblast cells. Mechanistically, circ_0001326 acted as a sponge for miR-188-3p, which directly targeted HTRA1. Moreover, circ_0001326 could regulate HTRA1 through sequestering miR-188-3p. A series of rescue experiments showed that miR-188-3p reversed the inhibitory effects of circ_0001326 knockdown on above behaviors of trophoblast cells. Besides that, HTRA1 silencing attenuated the action of miR-188-3p inhibitor on trophoblast cell phenotype alteration.

Conclusion: Our study demonstrated that circ_0001326 could promote trophoblast cell proliferation, invasion, migration and EMT in PE by miR-188-3p/HTRA1 axis, indicating a novel insight into the pathogenesis of PE.