Downregulated ribosomal protein L39 inhibits trophoblast cell migration and invasion by targeting E‐cadherin in the placenta of patients with preeclampsia

Jie, Qiuling; Sun, Fei; Li, Qi; Zhu, Jing; Wei, Yunjian; Yang, Huamei; Long, Ping; Wang, Zhen; Yang, Xiaohui; Ли, Дан; Huang, Liping; Ma, Yanlin

doi:10.1096/fj.202002061r

Cited by 11 publications

(11 citation statements)

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“…The in vitro experiments verified that tolcapone inhibits the migration and invasion of trophoblasts through changes in EMT signaling. Consistently, excessive E-cadherin hampered trophoblast invasion and has been implicated in patients with preeclampsia 25,26 . These findings suggest that tolcapone-induced productive and developmental toxicity share a similar mechanism of preeclampsia etiology.…”

Section: Discussionmentioning

confidence: 86%

COMT inhibitor tolcapone represses the migration and invasion of trophoblast and results in preeclampsia-like phenotypes in mice with the modulation of EMT signaling

Chen

Pang

Jie

et al. 2023

Preprint

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Pregnancy in young onset Parkinsons disease (YOPD) does not often occur, yet the medication in this condition is critical for maternal and fetal health. Tolcapone is an effective antiparkinsonian drug whereas the safety studies on mother and fetus are rather limited. In this study, we aimed to investigate the effects of tolcapone on mother and developing fetus in different gestations. Tolcapone was administrated to pregnant mice at the dose of 60 mg/kg/day (H-Tol) or 30 mg/kg/day (L-Tol), in the early gestation or the mid-gestation. We demonstrated that tolcapone in early gestation caused abortion and delayed fetus development in a dose-dependent manner. Taking tolcapone in mid-gestation barely caused embryo lethality, however, the mice developed preeclampsia-like phenotypes, including maternal hypertension, proteinuria and fetal growth restriction. The histomorphology analysis of placentas from tolcapone treated mice exhibited abnormalities in trophoblast layer and the hampered trophoblast invasion in decidua. In mechanistic study, we revealed that tolcapone inhibited the invasion and migration of trophoblast in vitro, with the changes in protein expressions of Snail, Twist and E-cadherin. In conclusion, tolcapone causes embryo lethality and growth restriction in early gestation, while in mid-gestation tolcapone causes preeclampsia-like phenotypes in mice with defective trophoblast invasion. Our study provides novel insight in understanding the effects of tolcapone in pregnancy.

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Section: Discussionmentioning

confidence: 86%

COMT inhibitor tolcapone represses the migration and invasion of trophoblast and results in preeclampsia-like phenotypes in mice with the modulation of EMT signaling

Chen

Pang

Jie

et al. 2023

Preprint

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“…Ribosome biogenesis and translation were particularly critical for cell growth and proliferation (48). Jie et al (49) reported that knockdown of ribosomal protein L39 (RPL39) inhibited the proliferation, migration, and invasion of trophoblast cells in vitro. APO was closely related to abnormal biological function of trophoblasts, since trophoblast cells were vital to placental and fetus development (50,51).…”

Section: Discussionmentioning

confidence: 99%

Potential genetic biomarkers predict adverse pregnancy outcome during early and mid-pregnancy in women with systemic lupus erythematosus

et al. 2022

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BackgroundEffectively predicting the risk of adverse pregnancy outcome (APO) in women with systemic lupus erythematosus (SLE) during early and mid-pregnancy is a challenge. This study was aimed to identify potential markers for early prediction of APO risk in women with SLE.MethodsThe GSE108497 gene expression dataset containing 120 samples (36 patients, 84 controls) was downloaded from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was performed, and differentially expressed genes (DEGs) were screened to define candidate APO marker genes. Next, three individual machine learning methods, random forest, support vector machine-recursive feature elimination, and least absolute shrinkage and selection operator, were combined to identify feature genes from the APO candidate set. The predictive performance of feature genes for APO risk was assessed using area under the receiver operating characteristic curve (AUC) and calibration curves. The potential functions of these feature genes were finally analyzed by conventional gene set enrichment analysis and CIBERSORT algorithm analysis.ResultsWe identified 321 significantly up-regulated genes and 307 down-regulated genes between patients and controls, along with 181 potential functionally associated genes in the WGCNA analysis. By integrating these results, we revealed 70 APO candidate genes. Three feature genes, SEZ6, NRAD1, and LPAR4, were identified by machine learning methods. Of these, SEZ6 (AUC = 0.753) showed the highest in-sample predictive performance for APO risk in pregnant women with SLE, followed by NRAD1 (AUC = 0.694) and LPAR4 (AUC = 0.654). After performing leave-one-out cross validation, corresponding AUCs for SEZ6, NRAD1, and LPAR4 were 0.731, 0.668, and 0.626, respectively. Moreover, CIBERSORT analysis showed a positive correlation between regulatory T cell levels and SEZ6 expression (P < 0.01), along with a negative correlation between M2 macrophages levels and LPAR4 expression (P < 0.01).ConclusionsOur preliminary findings suggested that SEZ6, NRAD1, and LPAR4 might represent the useful genetic biomarkers for predicting APO risk during early and mid-pregnancy in women with SLE, and enhanced our understanding of the origins of pregnancy complications in pregnant women with SLE. However, further validation was required.

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“…Recent studies showed that SLC6A9 [99], FKBP1B [100], S100A12 [101], SLC6A19 [102], TXN (thioredoxin) [103], TLR9 [104], HP (haptoglobin) [105], ARG1 [106], PINK1 [107], B2M [108], C5AR1 [109], MYADM (myeloid associated differentiation marker) [110], CBS (cystathionine beta-synthase) [111], GPX1 [112], SIAH2 [113], PRDX2 [114], RDH8 [115], CYP11B2 [116], RARRES2 [117], NOX1 [118], IL33 [119], OTC (ornithine transcarbamylase) [120], CYP1A1 [121], NFATC4 [122], TSLP (thymic stromal lymphopoietin) [123], WNT4 [124], MGP (matrix Gla protein) [125], FGFBP1 [126], GHR (growth hormone receptor) [127], ERBB3 [128], GFAP (glial fibrillary acidic protein) [129], CCDC40 [130], CACNB2 [131], CD34 [132], NOTCH3 [133], TERT (telomerase reverse transcriptase) [134], GNB3 [135], TP73 [136], RYR2 [137], ENPEP (glutamyl aminopeptidase) [138], SCN7A [139], WNK4 [140], SFRP5 [141], GDF15 [142], CAV1 [143], KCNA5 [144], FOXC1 [145], ASIC1 [146], VASH2 [147], CXCL8 [148], PAPPA2 [149], KCNMA1 [150], LOX (lysyl oxidase) [151], SPARCL1 [152] and CYP3A5 [153] might have the potential to be used as diagnostic biomarkers of hypertension. Previous studies have reported that RHD (Rh blood group D antigen) [154], S100A12 [155], TXN (thioredoxin) [156], TLR9 [157], S100P [158], TAGLN2 [159], S100A9 [160], CA1 [161], HP (haptoglobin) [162], RPL39 [163], F5 [164], PINK1 [165], B2M [166], S100A11 [167], SLC4A1 [168], CBS (cystathionine beta-sy...…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Genes and Biological Pathways in Bipolar Disorder by Bioinformatics and Next Generation Sequencing Data Analysis

Vastrad¹,

Vastrad²

2022

Preprint

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Bipolar disorder (BD), also known as psychiatric disorder, affects millions of people all over the world. The aim of this investigation was to screen and verify hub genes involved in BD as well as to explore potential molecular mechanisms. The next generation sequencing (NGS) dataset GSE124326 was downloaded from the Gene Expression Omnibus (GEO) database, which contained 480 samples, including 240 BD and 240 normal controls. Differentially expressed genes (DEGs) were filtered and subjected to gene ontology (GO) and pathway enrichment analyses. A protein–protein interaction (PPI) network and module analysis were used to identify hub genes. The miRNA-hub gene regulatory network and TF-hub gene regulatory network were also constructed. Receiver operating characteristic curve (ROC) analysis was used to validate hub genes. In this work, 957 DEGs, including 477 up regulated and 480 down regulated, were obtained from NGS data. The GO and pathway enrichment analyses of the DEGs showed that the up regulated genes were enriched in the neutrophil degranulation, immune system, transport, cytoplasm and enzyme regulator activity, and the down regulated genes were enriched in extracellular matrix organization, diseases of metabolism, multicellular organismal process, cell periphery and metal ion binding. Finally, through analyzing the PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network, we screened hub genes UBB, UBE2D1, TUBA1A, RPL11, RPS24, NOTCH3, CAV1, CNBD2, CCNA1 and MYH11 by the Cytoscape software. The current investigation illustrates a characteristic NGS data in BD, which might contribute to the interpretation of the progression of BD and provide novel biomarkers and therapeutic targets for BD.

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Downregulated ribosomal protein L39 inhibits trophoblast cell migration and invasion by targeting E‐cadherin in the placenta of patients with preeclampsia

Cited by 11 publications

References 41 publications

COMT inhibitor tolcapone represses the migration and invasion of trophoblast and results in preeclampsia-like phenotypes in mice with the modulation of EMT signaling

COMT inhibitor tolcapone represses the migration and invasion of trophoblast and results in preeclampsia-like phenotypes in mice with the modulation of EMT signaling

Potential genetic biomarkers predict adverse pregnancy outcome during early and mid-pregnancy in women with systemic lupus erythematosus

Identification of Key Genes and Biological Pathways in Bipolar Disorder by Bioinformatics and Next Generation Sequencing Data Analysis

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