The First School of Clinical Medicine, Southern Medical University, Guang Zhou, China.
Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou, China.
Reprod Sci. 2024 Nov;31(11):3428-3439. doi: 10.1007/s43032-024-01641-5. Epub 2024 Jul 12.
The aim of this study was to investigate the effects of miR-424-5p on biological behaviors and angiogenesis of the HTR-8/SVneo Cells. Our study included 60 parturient women, which were divided into an PA group (placenta accreta, n = 30) and a normal group (normal placenta, n = 30). QPCR was used to measure the expression of miR-424-5p in placental tissues. The effects of the miR-424-5p mimic on proliferation, migration, and invasion of human HTR-8/SVneo cells and angiogenesis were analyzed. The potential modulated relationship between miR-424-5p and low-density lipoprotein receptor-related protein-6 (LRP6) was demonstrated by luciferase assay. The expression of LRP6, β-catenin, matrix metalloproteinase-2 (MMP-2), placental growth factor (PGF) and vascular endothelial growth factor (VEGF) were measured by qPCR and Western blot assays. The expression of miR-424-5p in the PA group was significantly decreased than that in the normal group. The expression of miR-424-5p has negative correlation with blood loss. Upregulation of miR-424-5p significantly suppressed the cell proliferation, migration, and invasion of HTR-8/SVneo cells in vitro, as well as the tube formation of human umbilical vein endothelial cells (HUVECs). The luciferase assay demonstrated that LRP6 was a target of miR-424-5p. The expression of LRP6, β-catenin, MMP-2, PGF and VEGF were also decreased with upregulation of miR-424-5p (p < 0.05). The inhibitory effects of miR-424-5p on HTR-8/SVneo cells and angiogenesis were enhanced by downregulation of LRP6, but were reversed by upregulation of LRP6. The present study suggests that downregulation of miR-424-5p is related to the occurrence of PA. Enhancing miR-424-5p inhibits proliferation, migration, invasion and angiogenesis of the HTR-8/SVneo cells through targeting LRP6 mediated β-catenin, providing more insights about PA.
本研究旨在探讨 miR-424-5p 对 HTR-8/SVneo 细胞生物学行为和血管生成的影响。我们的研究纳入了 60 名产妇，分为胎盘侵袭组（PA 组，n=30）和正常胎盘组（n=30）。QPCR 用于测量胎盘组织中 miR-424-5p 的表达。分析 miR-424-5p 模拟物对人 HTR-8/SVneo 细胞增殖、迁移和侵袭以及血管生成的影响。通过荧光素酶测定证实了 miR-424-5p 与低密度脂蛋白受体相关蛋白-6（LRP6）之间的潜在调节关系。通过 qPCR 和 Western blot 测定测量了 LRP6、β-连环蛋白、基质金属蛋白酶-2（MMP-2）、胎盘生长因子（PGF）和血管内皮生长因子（VEGF）的表达。PA 组 miR-424-5p 的表达明显低于正常组。miR-424-5p 的表达与出血量呈负相关。上调 miR-424-5p 显著抑制 HTR-8/SVneo 细胞的体外增殖、迁移和侵袭以及人脐静脉内皮细胞（HUVEC）的管形成。荧光素酶测定表明 LRP6 是 miR-424-5p 的靶标。LRP6、β-连环蛋白、MMP-2、PGF 和 VEGF 的表达也随着 miR-424-5p 的上调而降低（p<0.05）。下调 LRP6 增强了 miR-424-5p 对 HTR-8/SVneo 细胞和血管生成的抑制作用，但上调 LRP6 则逆转了这种作用。本研究表明，miR-424-5p 的下调与 PA 的发生有关。通过靶向 LRP6 介导的β-连环蛋白增强 miR-424-5p 抑制 HTR-8/SVneo 细胞的增殖、迁移、侵袭和血管生成，为 PA 提供了更多的见解。
