Epithelial-mesenchymal transition process during embryo implantation

Oghbaei, Farnaz; Zarezadeh, Reza; Jafari-Gharabaghlou, Davoud; Ranjbar, Minoo; Nouri, Mohammad; Fattahi, Amir; Imakawa, Kazuhiko

doi:10.1007/s00441-021-03574-w

Cited by 22 publications

(16 citation statements)

References 153 publications

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“…Epithelial mesenchymal transformation (EMT), an important biological process, enables cells migratory and invasive capacity. 28 Herein, we further found that the circCRIM1/miR-942-5p/IL1RAP axis regulated the expression levels of EMT-related proteins (E-cadherin, Vimentin, and β-catenin) in trophoblast cells. In addition, IL1 signaling pathway was involved in diverse inflammatory and immune responses.…”

Section: Discussionmentioning

confidence: 61%

CircCRIM1 mediates proliferation, migration, and invasion of trophoblast cell through regulating miR‐942‐5p/IL1RAP axis

Xing

et al. 2023

American J Rep Immunol

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Background: Preeclampsia (PE) is a severe complication that occurs during pregnancy and a main cause of perinatal mortality of mothers as well as infants, which is characterized by abnormal placental trophoblast. Previous study reported that aberrant circular RNA (circRNA) was involved in the pathogenesis and progression of PE. Herein, we aimed to investigate the role of circCRIM1 and explore the mechanism of circCRIM1 in PE. Methods:The quantitative real-time PCR (qRT-PCR) was conducted to determine the relative expression of circCRIM1, miR-942-5p, and IL1RAP in tissues and cells. Cell proliferation viability was assessed by both MTT and EdU assays. Cell cycle distribution was analyzed using flow cytometry. Transwell assay was performed to test the cell migration and invasion. The protein levels of CyclinD1, MMP9, MMP2, and IL1RAP were measured by western blot. The putative binding sites between miR-942-5p and circCRIM1 or IL1RAP 3′UTR were verified by dual-luciferase reporter gene assay. Rescue experiment was performed to confirm that miR-942-5p/IL1RAP axis was functional target of circCRIM1 in trophoblast cells.Results: CircCRIM1 was upregulated in placenta tissues of PE and its expression was inversely related to infant weight. Overexpression of circCRIM1 suppressed proliferation, migration, and invasion and reduced the protein levels of CyclinD1, MMP9, MMP2 of trophoblast cells, whereas its knockdown exerted the opposite effect. CircCRIM1 could interact with miR-942-5p, and introduction of miR-942-5p partially abated the inhibitory effect of circCRIM1 on trophoblast cell behaviors. IL1RAP was directly targeted and negatively regulated by miR-942-5p. miR-942-5p played its regulatory role on cell proliferation, migration, and invasion of trophoblast by IL1RAP. Further analysis showed that circCRIM1 modulated IL1RAP expression via sponging miR-942-5p. Conclusion:The results of the present study demonstrated that circCRIM1 inhibited the proliferation, migration, and invasion of trophoblast cells through sponging miR-942-5p and up-regulating IL1RAP, providing a possible new mechanism of PE.

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Section: Discussionmentioning

confidence: 61%

CircCRIM1 mediates proliferation, migration, and invasion of trophoblast cell through regulating miR‐942‐5p/IL1RAP axis

Xing

et al. 2023

American J Rep Immunol

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“…Additionally, we checked the changes in the expression of genes related to epithelial-mesenchymal transition and extracellular matrix remodeling because these processes play a key role in trophoblast invasion ( Kaloglu and Onarlioglu 2010 ; Zhu et al 2012 ; Oghbaei et al 2022 ). The expression of mesenchymal marker genes N-cadherin ( CDH2 ), VIM , and ZEB1 was significantly decreased by NYNRIN KD ( fig.…”

Section: Resultsmentioning

confidence: 99%

Origination of LTR Retroelement–Derived NYNRIN Coincides with Therian Placental Emergence

Plianchaisuk

Kusama

Kato

et al. 2022

Molecular Biology and Evolution

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The emergence of the placenta is a revolutionary event in the evolution of therian mammals, to which some LTR retroelement-derived genes, such as PEG10, RTL1, and syncytin, are known to contribute. However, therian genomes contain many more LTR retroelement-derived genes that may also have contributed to placental evolution. We conducted large-scale evolutionary genomic and transcriptomic analyses to comprehensively search for LTR retroelement-derived genes whose origination coincided with therian placental emergence and that became consistently expressed in therian placentae. We identified NYNRIN as another Ty3/Gypsy LTR retroelement-derived gene likely to contribute to placental emergence in the therian stem lineage. NYNRIN knockdown inhibited the invasion of HTR8/SVneo invasive-type trophoblasts, whereas the knockdown of its non-retroelement-derived homolog KHNYN did not. Functional enrichment analyses suggested that NYNRIN modulates trophoblast invasion by regulating epithelial-mesenchymal transition and extracellular matrix remodeling and that the ubiquitin-proteasome system is responsible for the functional differences between NYNRIN and KHNYN. These findings extend our knowledge of the roles of LTR retroelement-derived genes in the evolution of therian mammals.

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“…This process is manifested by a change in cell polarity, remodeling of the cytoskeleton, the loss of epithelial markers, increased mesenchymal markers expression (vimentin and N-cadherin, etc.) and the gain of migration potential, all changes that are conducive to the invasion of trophoblastic cells [ 35 , 36 ]. In this study, we showed that YPEL3 inhibited vimentin expression in gEECs, but had no significant effect on the expression of N-cadherin, suggesting that YPEL3 affects endometrial function by inhibiting the EMT process.…”

Section: Discussionmentioning

confidence: 99%

YPEL3 Negatively Regulates Endometrial Function via the Wnt/β-Catenin Pathways during Early Pregnancy in Goats

Liu

Qiu

Liu

et al. 2022

Animals

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In ruminants, the establishment of pregnancy requires a series of structural and functional changes in the endometrium under the action of hormones, thereby providing an optimal environment for the implantation of the embryo. In this study, we explored the molecular mechanism by which YPEL3 regulates endometrial function during gestation in goats. We found YPEL3 expression was significantly downregulated during early gestation and that YPEL3 overexpression inhibited the expression of ISG15, but had no significant effects on the expression of RSAD2 and CXCL10 in goat endometrial epithelial cells (gEECs). In addition, YPEL3 silencing significantly inhibited PGF2α secretion and the expression of the prostaglandin synthesis-related rate-limiting enzyme-encoding genes PGFS and PTGES, with no significant effect on the expression of PTGS1 and PTGS2. Moreover, YPEL3 inhibited the expression of vimentin and β-catenin and pretreatment of gEECs with the β-catenin activator CHIR99021 prevented a YPEL3-induced decrease in vimentin expression. Collectively, our findings confirm that, as a hormone-regulated factor, YPEL3 regulates endometrial function by inhibiting the Wnt/β-catenin signaling pathway and provide new insights for further clarification of the mechanism by which YPEL3 functions during early pregnancy in ruminants.

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Epithelial-mesenchymal transition process during embryo implantation

Cited by 22 publications

References 153 publications

CircCRIM1 mediates proliferation, migration, and invasion of trophoblast cell through regulating miR‐942‐5p/IL1RAP axis

CircCRIM1 mediates proliferation, migration, and invasion of trophoblast cell through regulating miR‐942‐5p/IL1RAP axis

Origination of LTR Retroelement–Derived NYNRIN Coincides with Therian Placental Emergence

YPEL3 Negatively Regulates Endometrial Function via the Wnt/β-Catenin Pathways during Early Pregnancy in Goats

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