Journal
PLACENTA
Volume 103, Issue -, Pages 156-163Publisher
W B SAUNDERS CO LTD
DOI: 10.1016/j.placenta.2020.10.023
Keywords
Circ-AK2; miR-454-3p; THBS2; Preeclampsia; Biological behaviors
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This study showed that in preeclampsia, circ-AK2 inhibits the proliferation, migration, and invasion of trophoblast cells by targeting the miR-454-3p/THBS2 axis.
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-yl)-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.
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