miR-23a-3p increases endometrial receptivity via CUL3 during embryo implantation
miR-23a-3p increases endometrial receptivity via CUL3 during embryo implantation
复制标题
miR-23a-3p 在胚胎植入过程中通过 CUL3 增加子宫内膜容受性
DOI：
10.1530/jme-20-0053
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发表时间：
2020-08-01
影响因子：
3.5
通讯作者：
Hu, Linli
中科院分区：
文献类型：
--
作者：
Huang, Kai;Chen, Gezi;Hu, Linli
成功的胚胎着床需要一个可接受的子宫内膜。泛素化诱导的β -连环蛋白降解与植入失败有关。本研究旨在阐明miR-23a-3p是否通过调节β -连环蛋白泛素化来调节子宫内膜容受性。miR-23a-3p和CUL3在妊娠小鼠子宫内膜上皮细胞（EECs）和激素诱导的eec样Ishikawa细胞中表达。通过泛素化实验探讨CUL3和miR-23a-3p对β -连环蛋白泛素化水平的影响。将绒毛膜癌细胞系球体与石川细胞单层共培养，检测滋养细胞的附着。与妊娠第1天相比，妊娠第4天EECs以及激素诱导的Ishikawa细胞中miR-23a-3p上调，CUL3下调。miR-23a-3p正向调节β -catenin蛋白水平，但不影响mRNA水平。miR-23a-3p抑制β -连环蛋白的泛素化和降解，而CUL3促进β -连环蛋白的泛素化和降解。免疫沉淀证实CUL3与β -连环蛋白结合。荧光素酶报告基因检测证实了miR-23a-3p与CUL3之间的靶标关系。β -连环蛋白的泛素化可通过miR-23a-3p/CUL3途径调节。过表达miR-23a-3p促进石川细胞中的JAR球体附着。miR-23a-3p有利于子宫内膜容受性和胚胎着床，其机制部分是通过对CUL3/ β -连环蛋白的调节。
A receptive endometrium is required in a successful embryo implantation. The ubiquitination-induced beta-catenin degradation is related to the implantation failure. This study aimed to elucidate whether miR-23a-3p regulates endometrial receptivity via the modulation of beta-catenin ubiquitination.The expressions of miR-23a-3p and CUL3 were detected in endometrial epithelial cells (EECs) isolated from pregnant mice and in hormone-induced EEC-like Ishikawa cells. The ubiquitination experiment was performed to explore the effect of CUL3 and miR-23a-3p on beta-catenin ubiquitination level. The trophoblast attachment was detected by co-culturing JAR (choriocarcinoma cell line) spheroids with Ishikawa cell monolayers. miR-23a-3p was upregulated while CUL3 was downregulated in EECs at day 4 after pregnancy compared with day 1, as well as in hormone-induced Ishikawa cells. miR-23a-3p positively regulated the protein level of beta-catenin without affecting the mRNA level. The ubiquitination and degradation of beta-catenin was suppressed by miR-23a-3p, while it was promoted by CUL3. Immunoprecipitation confirmed the binding between CUL3 and beta-catenin. Luciferase reporter assay confirmed the target relationship between miR-23a-3p and CUL3. The ubiquitination of beta-catenin was modulated by the miR-23a-3p/CUL3 pathway. The overexpression of miR-23a-3p promoted JAR spheroid attachments in Ishikawa cells. miR-23a-3p is beneficial for the endometrial receptivity and embryo implantation, whose mechanism is partly through the modulation of CUL3/beta-catenin.