Yingqin Ye1, Mei Li2, Lu Chen3, Shuxian Li4, Zhengzhao Quan5. 1. Reproductive Medicine Center, Jingmen No.1 People's Hospital, Jingmen, Hubei, China. 2. Maternity Department, Jingmen No.1 People's Hospital, Jingmen, Hubei, China. 3. School of Clinical Medicine, Kunming Medical University, Kunming, Yunnan, China. 4. Postgraduate Training Basement of Jinzhou Medical University, Taihe Hospital Hubei University of Medicine, Shiyan, Hubei, China. 5. Maternity Department, Jingmen No.1 People's Hospital, Jingmen, Hubei, China. Electronic address: qaairr@163.com.
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.
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.