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miR-517-5p 的上调抑制 ERK/MMP-2 通路:子痫前期的潜在作用。

Up-regulation of miR-517-5p inhibits ERK/MMP-2 pathway: potential role in preeclampsia.

机构信息

Affiliated Hospital of Chengde Medical College, Chengde, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Oct;22(20):6599-6608. doi: 10.26355/eurrev_201810_16134.

Abstract

OBJECTIVE

To investigate the potential role of miRNA-517-5p in preeclampsia and its underlying mechanism.

MATERIALS AND METHODS

Placenta samples were obtained from 20 women with preeclampsia and 20 women with normal pregnancies. Expression level of miR-517-5p in placenta samples and JAR cells was detected. MiRNA-517-5p mimics or inhibitor was transfected in JAR cells, followed by detection of proliferative and invasive abilities of JAR cells. In addition, the expressions of extracellular regulated protein kinases (ERK), phospho-extracellular regulated protein kinases (p-ERK) and matrix metalloproteinase-2 (MMP-2) in JAR cells were evaluated by Western blot. Meanwhile, the mRNA level of MMP-2 was evaluated by Real-time polymerase chain reaction (PCR). The luciferase assay was applied to identify the target gene of miRNA-517-5p.

RESULTS

Increased level of miR-517-5p was detected in placenta samples of preeclampsia patients compared with normal pregnancies. MiRNA-517-5p could regulate proliferative and invasive abilities of JAR cells. Furthermore, miRNA-517-5p could regulate ERK/MMP-2 pathway in JAR cells, which would contribute to the pathophysiology of preeclampsia. The luciferase assay showed MMP-2 was the target gene of miR-517-5p. Further studies showed that MMP-2 was dysregulated in preeclampsia.

CONCLUSIONS

MiR-517-5p is highly expressed in placenta samples of preeclampsia pregnancies, which could promote proliferative and invasive abilities of JAR cells by inhibiting ERK/MMP-2 pathway.

摘要

目的

探讨 miRNA-517-5p 在子痫前期中的作用及其潜在机制。

材料与方法

收集 20 例子痫前期患者和 20 例正常妊娠患者的胎盘组织。检测胎盘组织和 JAR 细胞中 miR-517-5p 的表达水平。转染 miR-517-5p 模拟物或抑制剂于 JAR 细胞,检测 JAR 细胞的增殖和侵袭能力。此外,通过 Western blot 检测 JAR 细胞中细胞外调节蛋白激酶(ERK)、磷酸化细胞外调节蛋白激酶(p-ERK)和基质金属蛋白酶-2(MMP-2)的表达。同时,通过 Real-time PCR 检测 MMP-2 的 mRNA 水平。应用荧光素酶报告基因实验鉴定 miR-517-5p 的靶基因。

结果

与正常妊娠患者相比,子痫前期患者胎盘组织中 miR-517-5p 水平升高。miR-517-5p 可调节 JAR 细胞的增殖和侵袭能力。此外,miR-517-5p 可调节 JAR 细胞中的 ERK/MMP-2 通路,这可能有助于子痫前期的病理生理学过程。荧光素酶报告基因实验显示 MMP-2 是 miR-517-5p 的靶基因。进一步研究表明,MMP-2 在子痫前期中失调。

结论

miR-517-5p 在子痫前期患者胎盘组织中高表达,通过抑制 ERK/MMP-2 通路促进 JAR 细胞的增殖和侵袭。

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