PMID- 32474960 OWN - NLM STAT- MEDLINE DCOM- 20210402 LR - 20210402 IS - 1097-4652 (Electronic) IS - 0021-9541 (Linking) VI - 235 IP - 12 DP - 2020 Dec TI - miR-34a/c induce caprine endometrial epithelial cell apoptosis by regulating circ-8073/CEP55 via the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways. PG - 10051-10067 LID - 10.1002/jcp.29821 [doi] AB - 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. CI - (c) 2020 Wiley Periodicals LLC. FAU - Liu, Xiaorui AU - Liu X AD - College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China. FAU - Zhang, Lei AU - Zhang L AD - College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China. FAU - Yang, Lichun AU - Yang L AD - College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China. FAU - Cui, Jiuzeng AU - Cui J AD - College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China. FAU - Che, Sicheng AU - Che S AD - College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China. FAU - Liu, Yuexia AU - Liu Y AD - College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China. FAU - Han, Jincheng AU - Han J AD - College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China. FAU - An, Xiaopeng AU - An X AD - College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China. FAU - Cao, Binyun AU - Cao B AUID- ORCID: 0000-0002-9649-3246 AD - College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China. FAU - Song, Yuxuan AU - Song Y AUID- ORCID: 0000-0002-5302-7835 AD - College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200531 PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (Cell Cycle Proteins) RN - 0 (Cep55 protein, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Circular) RN - 0 (mTOR Associated Protein, LST8 Homolog) RN - EC 2.7.11.1 (raf Kinases) RN - EC 3.6.5.2 (ras Proteins) SB - IM MH - Animals MH - Apoptosis/*genetics MH - Cell Cycle Proteins/genetics MH - Embryo Implantation/*genetics MH - Endometrium/growth & development/metabolism MH - Epithelial Cells/metabolism MH - Female MH - Gene Expression Regulation, Developmental/genetics MH - Goats/genetics/growth & development MH - Humans MH - MicroRNAs/*genetics MH - RNA, Circular/*genetics MH - Signal Transduction/genetics MH - mTOR Associated Protein, LST8 Homolog MH - raf Kinases/genetics MH - ras Proteins/genetics OTO - NOTNLM OT - CEP55 OT - apoptosis OT - caprine endometrial epithelial cell OT - circ-8073 OT - miR-34a/c OT - receptive endometrium EDAT- 2020/06/01 06:00 MHDA- 2021/04/07 06:00 CRDT- 2020/06/01 06:00 PHST- 2019/09/25 00:00 [received] PHST- 2020/05/16 00:00 [revised] PHST- 2020/05/16 00:00 [accepted] PHST- 2020/06/01 06:00 [pubmed] PHST- 2021/04/07 06:00 [medline] PHST- 2020/06/01 06:00 [entrez] AID - 10.1002/jcp.29821 [doi] PST - ppublish SO - J Cell Physiol. 2020 Dec;235(12):10051-10067. doi: 10.1002/jcp.29821. Epub 2020 May 31.