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

机译:miR-183-5p部分通过靶向子痫前期的MMP-9抑制了HTR-8 / SVneo滋养层细胞的侵袭和迁移

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摘要

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.
机译:子痫前期(PE)是一种常见的产科疾病,其特征在于滋养层细胞的迁移和侵袭能力受损。据报道,MicroRNA-183-5p(miR-183)调节各种类型人类癌症中的细胞迁移和侵袭。然而,其在PE发病机理中的作用仍然难以捉摸。在本文中,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,孕妇胎盘组织中的miR-183明显上调。 miR-183的过表达抑制了HTR-8 / SVneo细胞的增殖,迁移和侵袭,并诱导了其凋亡。否则,miR-183的下调获得相反的效果。生物信息学预测和荧光素酶报告基因测定证实,基质金属蛋白酶9(MMP-9)是miR-183的靶标。此外,MPE-9的表达明显下调,并且与患有严重PE的孕妇胎盘组织中的miR-183水平呈负相关。 MMP-9的下调抑制了滋养层细胞的侵袭和迁移,而MMP-9的过表达促进了HTR-8 / SVneo细胞的侵袭和迁移。更重要的是,MMP-9的上调逆转了miR-183对滋养层细胞侵袭和迁移的抑制作用。总体而言,我们的发现表明,miR-183可能在PE的发病机制中起关键作用,并可能成为严重PE的潜在生物标志物。

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