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Endometrial Epithelial Cell Apoptosis Is Inhibited by a ciR8073-miR181a-Neurotensis Pathway during Embryo Implantation
Molecular Therapy - Nucleic Acids ( IF 6.5 ) Pub Date : 2018-12-14 , DOI: 10.1016/j.omtn.2018.12.005
Lei Zhang , Xiaorui Liu , Sicheng Che , Jiuzeng Cui , Xingna Ma , Xiaopeng An , Binyun Cao , Yuxuan Song

Development of the receptive endometrium (RE) from the pre-receptive endometrium (PE) is essential for embryo implantation, but its molecular mechanisms have not been fully understood. In this study, lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA networks were constructed to explore the functions of potential competing endogenous RNAs (ceRNA) during the development of RE in dairy goats. We observed that circRNA8073 (ciR8073) decreased the levels of miR-181a by acting as a miRNA sponge. This effect indirectly increased the expression of neurotensin in endometrial epithelial cells (EECs). Neurotensin then inhibited EEC apoptosis by increasing the expression of BCL-2/BAX in favor of BCL-2 via the MAPK pathway and also induced increased expression of leukemia-inhibitory factor, cyclo-oxygenase 2, vascular endothelial growth factor A, and homeobox A10. We have thus identified a ciR8073-miR181a-neurotensin pathway in the endometrium of dairy goats. Through this pathway, ciR8073 functions as a ceRNA that sequesters miR-181a, thereby protecting neurotensin transcripts from miR-181a-mediated suppression in EECs.



中文翻译:

ciR8073-miR181a-Neurotensis途径抑制子宫内膜上皮细胞凋亡。

从接受前子宫内膜(PE)发育到接受子宫内膜(RE)对于胚胎植入至关重要,但尚未完全了解其分子机制。在这项研究中,构建了lncRNA-miRNA-mRNA和circRNA-miRNA-mRNA网络,以探索乳山羊RE发育过程中潜在竞争内源RNA(ceRNA)的功能。我们观察到circRNA8073(ciR8073)通过充当miRNA海绵降低了miR-181a的水平。这种作用间接增加了子宫内膜上皮细胞(EECs)中神经降压素的表达。然后,神经降压素通过经由MAPK途径增加BCL-2 / BAX的表达来支持BCL-2来抑制EEC凋亡,并且还诱导了白血病抑制因子,环氧化酶2,血管内皮生长因子A和同源盒A10的表达增加。 。因此,我们在乳山羊的子宫内膜中鉴定了ciR8073-miR181a-神经降压素途径。通过此途径,ciR8073充当隔离miR-181a的ceRNA,从而保护神经降压素转录物免受miR-181a介导的EEC抑制。

更新日期:2018-12-14
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