Inhibition of Wilms’ Tumor Proliferation and Invasion by Blocking TGF-β Receptor I in the TGF-β/Smad Signaling Pathway

Shi, Qinlin; Wu, Huan; Li, Yonglin; Shen, Lianju; Tian, Xiaomao; Lin, Tao; Wei, Guanghui

doi:10.1155/2020/8039840

Cited by 8 publications

(6 citation statements)

References 32 publications

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“…This might indicate the potential action in TGFβ1 cytostatic effect in controlling cell proliferation but mediating EMT and invasion, as previously reported in WT (30,32,33). The dysregulation of TGFBβ has been linked to the initiation and progression of multiple human cancers, including WT (44).…”

Section: Discussionsupporting

confidence: 70%

Genetic Polymorphisms of the TGFB1 Signal Peptide and Promoter Region: Role in Wilms Tumor Susceptibility?

Ishibashi

Oliveira

Guembarovski

et al. 2021

jkcvhl

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The aim of the present study was to investigate the rs1800468 (G-800A), rs1800469 (C-509T), rs1800470 (C29T), and rs1800471 (G74C) TGFB1 genetic polymorphisms and their haplotype structures in patients with Wilms Tumor (WT) and neoplasia-free controls. The genomic DNA was extracted from 35 WT patients and 160 neoplasia-free children, and the TGFB1 polymorphisms were genotyped by polymerase chain reaction, followed by restriction fragment length polymorphism. The haplotype structures were inferred, and permutation and logistic regression tests were performed to check for differences in haplotype distribution between the control and WT individuals. Positive associations were found in the recessive model for rs1800469 T allele (OR: 8.417; 95% CI: 3.177 to 22.297; P < 0.001) and for the rs1800470 C allele (OR: 3.000; 95% CI: 1.296 to 6.944; P = 0.01). Haplotype analysis revealed a significant negative association between GCTG and WT (OR: 0.236, 95% CI: 0.105 to 0.534; P = 0.0002); by contrast, the GTTG haplotype was associated with increased risk for WT (OR: 12.0; 95% CI: 4.202 to 34.270; P < 0.001). Furthermore, rs1800469 was negatively correlated with tumor size and a trend toward a positive correlation for capsular invasion was observed in the dominant model (Tau-b: −0.43, P = 0.02 and tau-b: 0.5, P = 0.06, respectively). This is the first study with rs1800468, rs1800469, rs1800470, and rs1800471 TGFB1 polymorphisms in WT, and our results suggest that the TGFB1 promoter and signal peptide region polymorphisms may be associated with WT susceptibility and clinical presentation.

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Section: Discussionsupporting

confidence: 70%

Genetic Polymorphisms of the TGFB1 Signal Peptide and Promoter Region: Role in Wilms Tumor Susceptibility?

Ishibashi

Oliveira

Guembarovski

et al. 2021

jkcvhl

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“…Utilizing the MCODE app in Cytoscape software, five modules that might serve an important role in the development of Wilms tumor were detected. Studies have demonstrated the TGF-β/Smad signaling pathway plays a key role in Wilms tumor progression (25), while Li et al showed S1P/S1P1 signaling stimulates cell migration and invasion in the disease (26). Therefore, our KEGG and GO results suggest these signaling pathways may serve a crucial role in Wilms tumor progression.…”

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confidence: 60%

Bioinformatics analysis and identification of genes and pathways involved in patients with Wilms tumor

Li¹,

Tang²,

Huang³

et al. 2022

Transl Cancer Res TCR

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Background: Wilms tumor is the most common childhood kidney malignant tumor. However, the genes and signaling pathways associated with the disease remain incompletely understood.Methods: GSE66405, GSE73209, and GSE11151 were collected from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were detected using R software. A proteinprotein interaction (PPI) network was constructed using the STRING database, and the clustering modules and hub genes were analyzed with the Cytoscape software. Genes functional enrichment analyses were performed using the package "clusterProfiler" in R software, and the gene set enrichment analysis (GSEA) analysis was performed using GSEA v4.1.0 software.Results: Respectively, 3,092, 620, and 3,567 DEGs were screened in GSE66405, GSE73209, and GSE11151, with a total of 474 common DEGs detected in three expression profiles. For the common DEGs, the top 30 significant results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analyses were presented. Furthermore, five modules were found as the most related modules to Wilms tumor. GO term and KEGG pathway enrichment analyses of the genes in all the modules identified 10 GO terms and 5 KEGG pathways as significantly enriched. The top 10 hub DEGs of the PPI network were ALB, CDH1, EGF, AQP2, REN, SLC2A2, SPP1, UMOD, NPHS2, and FOXM1, with ALB identified as the highest degree. GSEA results showed 11 pathways were correlated with ALB expression in GSE66405 and 10 pathways were related to the expression of the ALB gene in GSE73209.Conclusions: Our study revealed robust gene signatures in Wilms tumor. Dysregulations of the signaling pathways were associated with the development and progression of the Wilms tumor, and 10 hub genes may play important roles in its diagnosis and therapy.

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“…Gene targets of miR-130a-3p were identified using miRNA target prediction databases, and we found that TGF-βRII was a possible target gene of miR-130a-3p. Previous studies showed that the TGF-β1 signaling pathway controls cell proliferation, differentiation, organ development, etc., by combing with TGF-βRII ( Shi et al, 2020 ). First, we examined whether miR-130a-3p downregulated TGF-βRII expression by Western blot and qRT-PCR ( Figures 5A–C ).…”

Section: Resultsmentioning

confidence: 99%

The miR-130a-3p/TGF-βRII Axis Participates in Inhibiting the Differentiation of Fibroblasts Induced by TGF-β1

et al. 2021

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Pulmonary fibrosis (PF) is a chronic progressive interstitial lung disease that has a poor prognosis. Abnormal activation of transforming growth factor-β1 (TGF-β1) plays a crucial role in fibroblast differentiation. Mesenchymal stem cells (MSCs) are currently being considered for the treatment of PF, but the regulatory mechanisms are poorly understood. We co-cultured bone marrow-derived MSCs and mouse lung fibroblasts (MLg) in the presence of TGF-β1, and studied the protein/mRNA expression of fibrosis markers and related signaling pathways. The effects of miR-130a-3p and TGF-β receptor II (TGF-βRII) on the differentiation of MLg induced by TGF-β1 were studied using immunofluorescence assay, Western blot, and quantitative real-time PCR techniques, respectively. Our results showed that MSCs reversed the overexpression of fibrosis markers and TGF-β1/Smad signaling pathway proteins and mRNAs after TGF-β1 treatment and increased the level of miR-130a-3p. TGF-βRII was identified as a target of miR-130a-3p and was evaluated by dual-luciferase reporter assay. The miR-130a-3p/TGF-βRII axis could suppress the differentiation of lung fibroblasts via the TGF-β1/Smad signaling pathway, thereby reducing the process of PF.

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Inhibition of Wilms’ Tumor Proliferation and Invasion by Blocking TGF-β Receptor I in the TGF-β/Smad Signaling Pathway

Cited by 8 publications

References 32 publications

Genetic Polymorphisms of the TGFB1 Signal Peptide and Promoter Region: Role in Wilms Tumor Susceptibility?

Genetic Polymorphisms of the TGFB1 Signal Peptide and Promoter Region: Role in Wilms Tumor Susceptibility?

Bioinformatics analysis and identification of genes and pathways involved in patients with Wilms tumor

The miR-130a-3p/TGF-βRII Axis Participates in Inhibiting the Differentiation of Fibroblasts Induced by TGF-β1

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