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核因子-κB 诱导的 microRNA-518a-5p 通过核因子-κB 通路抑制滋养细胞迁移和侵袭。

Nuclear Factor-Kappa B-induced miRNA-518a-5p represses trophoblast cell migration and invasion by the Nuclear Factor-Kappa B pathway.

机构信息

Department of Gynaecology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian 223300, Jiangsu, China.

Department of Pathology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian 223300, Jiangsu, China.

出版信息

An Acad Bras Cienc. 2023 May 1;95(1):e20220596. doi: 10.1590/0001-3765202320220596. eCollection 2023.

Abstract

Preeclampsia is associated with the insufficient invasion of trophoblasts. NF-κB is a transcription factor in almost all mammalian cells and has been validated to be upregulated in the maternal circulation and placenta of women with preeclampsia. MiR-518a-5p is also overexpressed in pre-eclamptic placenta. The present study was designed to explore whether NF-κB can transcriptionally activate miR-518a-5p and investigate the influences of miR-518a-5p on the viability, apoptosis, migration, and invasion of HTR8/SVneo trophoblast. In situ hybridization and real time polymerase chain reaction were used to reveal miR-518a-5p expression in placenta tissues and HTR8/SVneo cells, respectively. Cell migration and invasion were detected using Transwell inserts. Our findings indicated that NF-κB p52, p50, and p65 can bind to miR-518a-5p gene promoter. MiR-518a-5p further influences the levels of p50 and p65 but not p52. HTR8/SVneo cell viability and apoptosis were not influenced by miR-518a-5p. However, miR-518a-5p represses the migratory/invasive capacities of HTR8/SVneo cell and decreased gelatinolytic activity of MMP2 and MMP9, which was reversed by an NF-κB inhibitor. To sum up, miR-518a-5p is induced by NF-κB and represses trophoblast cell migration and invasion by the NF-κB pathway.

摘要

子痫前期与滋养细胞浸润不足有关。NF-κB 是几乎所有哺乳动物细胞中的转录因子,已被证实其在子痫前期妇女的母体循环和胎盘组织中上调。miR-518a-5p 在子痫前期胎盘组织中也过表达。本研究旨在探讨 NF-κB 是否可以转录激活 miR-518a-5p,并研究 miR-518a-5p 对 HTR8/SVneo 滋养细胞活力、凋亡、迁移和侵袭的影响。原位杂交和实时聚合酶链反应分别用于揭示胎盘组织和 HTR8/SVneo 细胞中 miR-518a-5p 的表达。使用 Transwell 插入物检测细胞迁移和侵袭。我们的研究结果表明,NF-κB p52、p50 和 p65 可以与 miR-518a-5p 基因启动子结合。miR-518a-5p 进一步影响 p50 和 p65 的水平,但不影响 p52。miR-518a-5p 不影响 HTR8/SVneo 细胞的活力和凋亡。然而,miR-518a-5p 抑制 HTR8/SVneo 细胞的迁移/侵袭能力,并降低 MMP2 和 MMP9 的明胶酶活性,NF-κB 抑制剂可逆转这种作用。总之,miR-518a-5p 受 NF-κB 诱导,并通过 NF-κB 途径抑制滋养细胞的迁移和侵袭。

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