MiR-23a-3p increases endometrial receptivity via CUL3 during embryo implantation. (August 2020)

• Record Type: Journal Article
• Authors: Huang, Kai; Chen, Gezi; Fan, Wenqian; Hu, Linli
• Is Part Of: Journal of molecular endocrinology. Volume 65:Number 2(2020)
• Page Start: 35
• Page End: 44
• Publication Date: 2020-08
• Subjects: embryo implantation -- endometrial receptivity -- ubiquitination -- CUL3 -- miR-23a-3p; Molecular endocrinology -- Periodicals; Endocrinology -- Periodicals; 616.407
• DOI: 10.1530/JME-20-0053
• Languages: English
• ISSNs: 0952-5041

Abstract

Abstract : A receptive endometrium is required in a successful embryo implantation. The ubiquitination-induced β-catenin degradation is related to the implantation failure.This study aimed to elucidate whether miR-23a-3p regulates endometrial receptivity via the modulation of β-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 β-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 β-catenin without affecting the mRNA level. The ubiquitination and degradation of β-catenin was suppressed by miR-23a-3p, while it was promoted by CUL3. Immunoprecipitation confirmed the binding between CUL3 and β-catenin. Luciferase reporter assay confirmed the target relationship between miR-23a-3p and CUL3. The ubiquitination of β-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/β-catenin.