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miR-183-5p 通过靶向 MMP-9 部分抑制子痫前期 HTR-8/SVneo 滋养细胞的侵袭和迁移。

miR-183-5p suppressed the invasion and migration of HTR-8/SVneo trophoblast cells partly via targeting MMP-9 in preeclampsia.

机构信息

Department of Obstetrics and Gynecology, The First Hospital of Shanxi Medical University, Taiyuan 030001, China.

出版信息

Biosci Rep. 2020 Jun 26;40(6). doi: 10.1042/BSR20192575.

Abstract

Preeclampsia (PE), a common obstetrical disorder, is characterized by impaired migration and invasion abilities of trophoblastic cells. MicroRNA-183-5p (miR-183) was reported to regulate cell migration and invasion in various types of human cancers; however, its role in the pathogenesis of PE remains elusive. Herein, we investigated the role of miR-183 in HTR-8/SVneo trophoblast cells invasion and migration and explored the underlying mechanism. Our results showed that miR-183 was significantly up-regulated in placental tissues from pregnant women compared with that in normal pregnant women. Overexpression of miR-183 inhibited proliferation, migration and invasion, as well as induced apoptosis in HTR-8/SVneo cells. Otherwise, down-regulation of miR-183 achieved the opposite effects. Bioinformatics prediction and luciferase reporter assay confirmed that matrix metalloproteinase-9 (MMP-9) is a target of miR-183. In addition, MMP-9 expression was significantly down-regulated, and inversely correlated with the miR-183 level in placental tissues from pregnant women with severe PE. Down-regulation of MMP-9 suppressed the trophoblast cell invasion and migration, whereas overexpression of MMP-9 promoted cell invasion and migration in HTR-8/SVneo cells. More importantly, up-regulation of MMP-9 reversed the inhibitory effects of miR-183 on cell invasion and migration in trophoblast cells. Collectively, our findings suggested that miR-183 may play critical roles in the pathogenesis of PE and serve as a potential biomarker for severe PE.

摘要

子痫前期(PE)是一种常见的产科疾病,其特征是滋养细胞的迁移和侵袭能力受损。miR-183-5p(miR-183)已被报道可调节多种人类癌症中的细胞迁移和侵袭;然而,其在 PE 发病机制中的作用仍不清楚。在此,我们研究了 miR-183 在 HTR-8/SVneo 滋养细胞侵袭和迁移中的作用,并探讨了其潜在机制。我们的结果表明,与正常孕妇相比,孕妇胎盘组织中 miR-183 显著上调。miR-183 的过表达抑制了 HTR-8/SVneo 细胞的增殖、迁移和侵袭,并诱导了细胞凋亡。相反,下调 miR-183 则产生了相反的效果。生物信息学预测和荧光素酶报告基因实验证实 MMP-9 是 miR-183 的靶基因。此外,在患有严重 PE 的孕妇的胎盘组织中,MMP-9 的表达显著下调,并且与 miR-183 的水平呈负相关。下调 MMP-9 抑制了滋养细胞的侵袭和迁移,而 MMP-9 的过表达则促进了 HTR-8/SVneo 细胞的侵袭和迁移。更重要的是,下调 MMP-9 逆转了 miR-183 对滋养细胞侵袭和迁移的抑制作用。综上所述,我们的研究结果表明,miR-183 在 PE 的发病机制中可能发挥关键作用,并可能作为严重 PE 的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6494/7273907/f7433acb4e4a/bsr-40-bsr20192575-g1.jpg

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