Downregulation of miR-29a/b/c in placenta accreta inhibits apoptosis of implantation site intermediate trophoblast cells by targeting MCL1
Downregulation of miR-29a/b/c in placenta accreta inhibits apoptosis of implantation site intermediate trophoblast cells by targeting MCL1
复制标题
侵入性胎盘中 miR-29a/b/c 的下调通过靶向 MCL1 抑制植入部位中间滋养层细胞的凋亡。
DOI：
10.1016/j.placenta.2016.09.017
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发表时间：
2016-12-01
期刊：
影响因子：
3.8
通讯作者：
Chen, Zi-Jiang
中科院分区：
文献类型：
--
作者：
Gu, Yongzhong;Bian, Yuehong;Chen, Zi-Jiang
目的：胎盘植入是指胎盘绒毛与子宫肌层的异常粘连。虽然这种情况已成为越来越常见的剖宫产率的结果，潜在的致病机制（S）仍然难以捉摸。由于microRNA-29 a/B/c（miR-29 a/B/c）已被证明在胎盘发育中发挥重要作用，因此本研究评估了这些microRNA在胎盘植入中的作用。方法：使用实时定量聚合酶链反应定量患者组织和HTR 8/SVneo滋养层细胞中miR-29 a/B/c和骨髓细胞白血病-1（MCL 1）的表达。采用Western印迹法分析miR-29 a/B/c表达改变的HTR 8/SVneo滋养层细胞中MCL 1蛋白的表达。为了确定它们在凋亡中的作用，miR-29 a/B/c在HTR-8/SVneo细胞中过表达，并通过流式细胞术分析凋亡水平。荧光素酶活性测定用于确定MCL 1是否是miR-29 a/B/c的靶基因。结果：与非creta位点相比，creta位点中miR-29 a/B/c的表达显著降低（分别为p = 0.018、0.041和0.022），但在creta位点中MCL 1的表达上调（p = 0.039）。在过表达miR-29 a/B/c的HTR-8/SVneo细胞中，MCL 1表达显著下调（分别为p = 0.002、0.008和0.013）。荧光素酶活性测定显示miR-29 a/bic直接靶向293 T细胞中MCL 1的3'非翻译区。miR-29 a/B/c过表达诱导HTR-8/SVneo滋养层细胞系凋亡结论：miR-29 a/B/c通过靶向MCL 1抑制胎盘植入部位中间滋养层细胞（ISIT）凋亡。这些发现为胎盘植入的发病机制提供了新的见解。(C)2016爱思唯尔有限公司版权所有
Objective: Placenta accreta is defined as abnormal adhesion of placental villi to the uterine myometrium. Although this condition has become more common as a result of the increasing rate of cesarean sections, the underlying causative mechanism(s) remain elusive. Because microRNA-29a/b/c (miR-29a/b/c) have been shown to play important roles in placental development, this study evaluated the roles of these microRNAs in placenta accreta.Methods: Expression of miR-29a/b/c and myeloid cell leukemia-1 (MCL1) were quantified in patient tissues and HTR8/SVneo trophoblast cells using the real-time quantitative polymerase chain reaction. Western blotting was used to analyze expression of the MCL1 protein in HTR8/SVneo trophoblast cells with altered expression of miR-29a/b/c. To determine their role in apoptosis, miR-29a/b/c were over expressed in HTR-8/SVneo cells, and levels of apoptosis were analyzed by flow cytometry. Luciferase activity assays were used to determine whether MCL1 is a target gene of miR-29a/b/c.Results: Expression of miR-29a/b/c was significantly lower in creta sites compared to noncreta sites (p = 0.018, 0.041, and 0.022, respectively), but expression of MCL1 was upregulated in creta sites (p = 0.039). MCL1 expression was significantly downregulated in HTR-8/SVneo cells overexpressing miR-29a/b/c (p = 0.002, 0.008, and 0.013, respectively). Luciferase activity assays revealed that miR-29a/bic directly target the 3' untranslated region of MCL1 in 293T cells. Over-expression of miR-29a/b/c induced apoptosis in the HTR-8/SVneo trophoblast cell line. Moreover, histopathological evaluation revealed that the number of implantation site intermediate trophoblast (ISIT) cells was increased in creta sites and that these cells were positive for MCL1.Conclusions: Our results demonstrate that in placenta accreta, miR-29a/b/c inhibits apoptosis of ISIT cells by targeting MCL1. These findings provide new insights into the pathogenesis of placenta accreta. (C) 2016 Elsevier Ltd. All rights reserved.