MiR-519d-3p suppresses invasion and migration of trophoblast cells via targeting MMP-2.
MiR-519d-3p suppresses invasion and migration of trophoblast cells via targeting MMP-2.
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MiR-519d-3p 通过靶向 MMP-2 抑制滋养层细胞的侵袭和迁移
DOI：
10.1371/journal.pone.0120321
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Zhu X
中科院分区：
文献类型：
--
作者：
Ding J;Huang F;Wu G;Han T;Xu F;Weng D;Wu C;Zhang X;Yao Y;Zhu X
本研究经第四军医大学唐都医院医学伦理委员会批准，严格遵守国家伦理准则。先兆子痫（PE）是一种以妊娠期高血压和蛋白尿为特征的特殊临床疾病，是全球孕产妇和围产儿死亡的主要原因。miR-519 d-3 p在PE患者的母体血浆中上调，这表明该microRNA与PE的发病机制之间可能存在关联。迄今为止，还没有研究涉及miR-519 d-3 p对滋养层细胞侵袭和迁移的影响。在我们的研究中，我们发现miR-519 d-3 p在PE患者的胎盘样本中表达升高。在体外，miR-519 d-3 p的过表达显著抑制滋养层细胞的迁移和侵袭，而miR-519 d-3 p抑制剂的转染增强滋养层细胞的迁移和侵袭。荧光素酶分析证实基质金属蛋白酶-2（MMP-2）是miR-519 d-3 p的直接靶点。实时荧光定量PCR和Western blot检测显示，miR-519 d-3 p过表达可下调MMP-2 mRNA和蛋白表达。使用siRNA敲低MMP-2减弱了miR-519 d-3 p抑制剂促进的滋养层迁移和侵袭增加。在PE患者或正常妊娠的胎盘中，使用Pearson相关性和线性回归分析观察到MMP-2和miR-519 d-3 p的表达之间呈负相关。我们目前的研究结果表明，上调miR-519 d-3 p可能有助于通过抑制滋养层细胞的迁移和侵袭通过靶向MMP-2的PE的发展; miR-519 d-3 p可能代表一个潜在的预测和治疗PE的目标。
Our study was approved by the Medical Ethics Committee of Tang Du Hospital, Fourth Military Medical University and complied strictly with national ethical guidelines. Preeclampsia (PE) is a specific clinical disorder characterized by gestational hypertension and proteinuria and is a leading cause of maternal and perinatal mortality worldwide. The miR-519d-3p is upregulated in the maternal plasma of patients with PE which indicates a possible association between this microRNA and the pathogenesis of PE. No studies to date have addressed the effect of miR-519d-3p on the invasion and migration of trophoblast cells. In our study, we found that miR-519d-3p expression was elevated in placental samples from patients with PE. In vitro, overexpression of miR-519d-3p significantly inhibited trophoblast cell migration and invasion, whereas transfection of a miR-519d-3p inhibitor enhanced trophoblast cell migration and invasion. Luciferase assays confirmed that matrix metalloproteinase-2 (MMP-2) is a direct target of miR-519d-3p. Quantitative real-time PCR and western blot assays showed that overexpression of miR-519d-3p downregulated MMP-2 mRNA and protein expression. Knockdown of MMP-2 using a siRNA attenuated the increased trophoblast migration and invasion promoted by the miR-519d-3p inhibitor. In placentas from patients with PE or normal pregnancies, a negative correlation between the expression of MMP-2 and miR-519d-3p was observed using the Pearson correlation and linear regression analysis. Our present findings suggest that upregulation of miR-519d-3p may contribute to the development of PE by inhibiting trophoblast cell migration and invasion via targeting MMP-2; miR-519d-3p may represent a potential predictive and therapeutic target for PE.
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DOI：
10.1038/nrneph.2014.102
发表时间：
2014-08
期刊：
Nature reviews. Nephrology
影响因子：
--
作者：
Chaiworapongsa T;Chaemsaithong P;Yeo L;Romero R
通讯作者：
Romero R
影响因子：
3.8
作者：
Morales-Prieto, D. M.;Chaiwangyen, W.;Markert, U. R.
通讯作者：
Markert, U. R.
影响因子：
7.3
作者：
Hsu P;Nanan RK
通讯作者：
Nanan RK
影响因子：
4
作者：
Pang Y;Mao H;Shen L;Zhao Z;Liu R;Liu P
通讯作者：
Liu P
影响因子：
7.3
作者：
Fornari, Francesca;Milazzo, Maddalena;Gramantieri, Laura
通讯作者：
Gramantieri, Laura