Down-regulation of miR-378a-3p induces decidual cell apoptosis: a possible mechanism for early pregnancy loss
Down-regulation of miR-378a-3p induces decidual cell apoptosis: a possible mechanism for early pregnancy loss
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miR-378a-3p 下调诱导蜕膜细胞凋亡：早期妊娠流产的可能机制
DOI：
10.1093/humrep/dex347
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发表时间：
2018-01-01
影响因子：
6.1
通讯作者：
Huang, Hefeng
中科院分区：
文献类型：
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作者：
Hong, Lihua;Yu, Tiantian;Huang, Hefeng
microRNA (miRNA) 是否会导致人类早期妊娠丢失 (EPL)？miR-378a-3p 表达受孕酮调节，在 EPL 患者的蜕膜中表达下调，可能通过 Caspase-3 激活导致蜕膜细胞凋亡。多种 miRNA 已被证明与蜕膜化和胎盘形成的发展有关。然而，关于miRNA在EPL发病机制中的作用鲜有报道。分别从正常妊娠选择性终止妊娠患者和EPL患者中采集正常和EPL蜕膜组织。利用miRNA芯片鉴定正常和EPL蜕膜之间差异表达的miRNA，并通过qRT-PCR、qRT-PCR、Western blotting和荧光素酶报告基因检测证实miRNA的表达。验证 miR-378a-3p 的下游靶标。使用miR-378a-3p转染的蜕膜细胞评估miR-378a-3p的作用。值得注意的是，当将EPL与正常蜕膜进行比较时，通过微阵列分析鉴定出32个上调的miRNA和38个下调的miRNA。 MiR-378a-3p 在 EPL 蜕膜中显着下调，并被发现通过直接结合 Caspase-3 的 3'-UTR 来反向调节 Caspase-3 的表达。在蜕膜细胞中，转染 miR-378a-3p 模拟物可抑制细胞凋亡，并通过抑制 Caspase-3 增加细胞增殖。此外，我们发现黄体酮可以诱导蜕膜细胞中miR-378a-3p的表达。本研究重点关注miR-378a-3p及其靶标Caspase-3的功能，然而，许多其他靶标和miRNA也可能与EPL的发病机制有关。因此，需要进一步的研究来阐明miRNA在EPL中的作用。我们的研究结果表明，miR-378a-3p可能有助于EPL的发展，并且它可以作为黄体酮治疗EPL的新的潜在预测和治疗靶点。该研究得到了国家基础研究计划（No.2012CB944900）的支持；国家自然科学基金项目（No.31471405、81490742、No.81361120246）；国家科技支撑计划项目（No.2012BA132B00）。作者声明没有竞争利益。
Do microRNAs (miRNAs) contribute to human early pregnancy loss (EPL)?miR-378a-3p expression is regulated by progesterone and is down-regulated in ducidua of EPL patients which may contribute to decidual apoptosis through Caspase-3 activation.A variety of miRNAs have been demonstrated to be associated with the development of decidualization and placental formation. However, little has been reported on the roles of miRNA in the pathogenesis of EPL.Normal and EPL decidual tissues were collected from patients with normal pregnancies undergoing elective termination of gestation, and from patients with EPL, respectively.miRNA microarrays were used to identify the differentially expressed miRNAs between normal and EPL decidua, and miRNA expression was confirmed by qRT-PCR, qRT-PCR, western blotting and luciferase reporter assays were employed to validate the downstream targets of miR-378a-3p. The effects of miR-378a-3p were evaluated using miR-378a-3p-transfected decidual cells.Of note, 32 up-regulated miRNAs and 38 down-regulated miRNAs were identified by microarray analysis when comparing EPL to normal decidua. MiR-378a-3p was significantly down-regulated in the EPL decidua and was found to inversely regulate the expression of Caspase-3 by directly binding to its 3'-UTRs. In decidual cells, transfection of miR-378a-3p mimics resulted in the inhibition of cell apoptosis and in the increase of cell proliferation through Caspase-3 suppression. Moreover, we found that progesterone could induce the expression of miR-378a-3p in decidual cells.This study focused on the function of miR-378a-3p and its target Caspase-3, however, numerous other targets and miRNAs may also be responsible for the pathogenesis of EPL. Therefore, further studies are required to elucidate the role of miRNAs in EPL.Our findings indicate that miR-378a-3p may contribute to the development of EPL, and that it could serve as a new potential predictive and therapeutic target of progesterone-treatment for EPL.This study was supported by National Basic Research Program of China (No.2012CB944900); National Science Foundation of China (No.31471405 and 81490742, No.81361120246); The National Science and Technology Support Program (No.2012BA132B00). Authors declare no competing interests.