Circ-AK2 is associated with preeclampsia and regulates biological behaviors of trophoblast cells through miR-454-3p/THBS2

Abstract

Introduction: Circ-AK2 has been found to be differentially expressed in PE placenta tissues, however, the role and the underlying molecular mechanisms of circ-AK2 in PE remain poorly known.

Methods: The expression of circ-AK2, miR-454-3p, and THBS2 mRNA was detected using quantitative real-time polymerase chain reaction. Protein levels of CyclinD1, MMP-9 and THBS2 were measured using Western blot. Cell proliferation, migration, and invasion were analyzed by 3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-di-phenytetrazoliumromide (MTT) assay and transwell assay. The interaction between miR-454-3p and circ-AK2 or THBS2 was analyzed by the dual-luciferase reporter assay.

Results: Circ-AK2 was highly expressed in placental tissues of PE, and overexpression of circ-AK2 inhibited trophoblast cell proliferation, migration and invasion. Circ-AK2 directly bound to miR-454-3p, and miR-454-3p overexpression reversed the inhibitory action of circ-AK2 in biological functions of trophoblast cells. MiR-454-3p was lowly expressed in placental tissues of PE, and directly regulated THBS2 expression in a targeted manner. Silencing miR-454-3p suppressed the proliferating, migratory, and invasive abilities of trophoblast cells, while this condition was abolished by THBS2 knockdown. Besides, we also proved circ-AK2 could regulate THBS2 expression via miR-454-3p.

Discussion: Circ-AK2 inhibited the proliferation, migration and invasion of trophoblast cells via targeting miR-454-3p/THBS2 axis, suggesting a novel insight into the etiology of PE and a potential therapeutic target for PE treatment.

Keywords: Biological behaviors; Circ-AK2; Preeclampsia; THBS2; miR-454–3p.