College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
J Cell Physiol. 2020 Dec;235(12):10051-10067. doi: 10.1002/jcp.29821. Epub 2020 May 31.
microRNAs (miRNAs) and circular RNAs (circRNAs) are important for endometrial receptivity establishment and embryo implantation in mammals. miR-34a and miR-34c are highly expressed in caprine receptive endometrium (RE). Herein, the functions and mechanisms of miR-34a/c in caprine endometrial epithelial cell (CEEC) apoptosis and RE establishment were investigated. miR-34a/c downregulated the expression level of centrosomal protein 55 (CEP55) and were sponged by circRNA8073 (circ-8073), thereby exhibiting a negative interaction in CEEC. miR-34a/c induced CEEC apoptosis by targeting circ-8073/CEP55 through the regulation of the RAS/RAF/MEK/ERK and phosphoitide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways. Positive and negative feedback loops and cross-talk were documented between the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways. miR-34a/c regulated the levels of RE marker genes, including forkhead box M1, vascular endothelial growth factor, and osteopontin (OPN). These results suggest that miR-34a/c not only induce CEEC apoptosis by binding to circ-8073 and CEP55 via the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways, but may also regulate RE establishment in dairy goats.
微小 RNA（miRNA）和环状 RNA（circRNA）在哺乳动物的子宫内膜容受性建立和胚胎植入中起着重要作用。miR-34a 和 miR-34c 在山羊接受性子宫内膜（RE）中高表达。在此，研究了 miR-34a/c 在山羊子宫内膜上皮细胞（CEEC）凋亡和 RE 建立中的功能和机制。miR-34a/c 下调中心体蛋白 55（CEP55）的表达水平，并被环状 RNA8073（circ-8073）海绵吸附，从而在 CEEC 中表现出负相互作用。miR-34a/c 通过调节 RAS/RAF/MEK/ERK 和磷酸肌醇 3-激酶（PI3K）/蛋白激酶 B（AKT）/雷帕霉素靶蛋白（mTOR）通路，通过靶向 circ-8073/CEP55 诱导 CEEC 凋亡。RAS/RAF/MEK/ERK 和 PI3K/AKT/mTOR 通路之间存在正反馈和负反馈回路以及串扰。miR-34a/c 调节 RE 标记基因的水平，包括叉头框 M1、血管内皮生长因子和骨桥蛋白（OPN）。这些结果表明，miR-34a/c 不仅通过 RAS/RAF/MEK/ERK 和 PI3K/AKT/mTOR 通路与 circ-8073 和 CEP55 结合诱导 CEEC 凋亡，而且可能调节奶山羊的 RE 建立。
