MicroRNA Profiling in Wilms Tumors and Kidney Tissues
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE50505 | GEO | 2013/12/22
SECONDARY ACCESSION(S): PRJNA217783
REPOSITORIES: GEO
Similar Datasets
Project description:The IGF2-intronic miR-483 selectively enhances transcription from IGF2 fetal promoters and enhances tumorigenesis. The expression levels of microRNAs were profiled in 20 human Wilms tumor samples (WT), 3 human normal adult kidney samples (AK) and 5 human fetal kidney samples (FK) using a Luminex bead platform.
2013-12-22 | E-GEOD-50505 | biostudies-arrayexpress
Project description:Changes in microRNA expression in Igf2-p and H19-m mouse embryos (E9.5) were determined in order to assess whether perturbation of miR-483* and miR-675 in Igf2-p and H19-m mutants was likely to have contributed to a modification of tumour phenotype. The Igf2 gene contains miR-483* but the targeted deletion of Igf2-p in these mice spares the region encoding this microRNA. The H19 gene contains miR-675 and its expression was mono-allelelic in heterozygous H19-m mice as evidenced by a significant reduction in miR-675 in these mice relative to WT.
2011-12-01 | E-MTAB-873 | biostudies-arrayexpress
Project description:Numerous studies have described the critical role played by microRNAs (miRNAs) in cancer progression and the potential of these small non-coding RNAs for diagnostic or therapeutic applications. However, the mechanisms responsible for the altered expression of miRNAs in malignant cells remain poorly understood. Herein, via epigenetic unmasking, we identified a group of miRNAs located in the imprinted delta like non-canonical Notch ligand 1 (DLK1)-maternally expressed 3 (MEG3) locus that were repressed in hepatic tumor cells. Notably, miR-493-5p epigenetic silencing was correlated with hypermethylation of the MEG3-differentially regulated region (DMR) in liver cancer cell lines and tumor tissues from patients. Experimental rescue of miR-493-5p promoted an anti-cancer response by hindering hepatocellular carcinoma (HCC) cell growth in vitro and tumor progression in vivo. We found that miR-493-5p mediated part of its tumor-suppressor activity by abrogating overexpression of insulin-like growth factor 2 (IGF2) and the IGF2-derived intronic oncomir miR-483-3p in HCC cells characterized by IGF2 loss of imprinting (LOI). In summary, this study describes an unknown miRNA-dependent regulatory mechanism between two distinct imprinted loci and a possible therapeutic window for liver cancer patients exhibiting IGF2-miR-483 LOI and amplification.
2018-12-05 | GSE123313 | GEO
Project description:Numerous studies have described the critical role played by microRNAs (miRNAs) in cancer progression and the potential of these small non-coding RNAs for diagnostic or therapeutic applications. However, the mechanisms responsible for the altered expression of miRNAs in malignant cells remain poorly understood. Herein, via epigenetic unmasking, we identified a group of miRNAs located in the imprinted delta like non-canonical Notch ligand 1 (DLK1)-maternally expressed 3 (MEG3) locus that were repressed in hepatic tumor cells. Notably, miR-493-5p epigenetic silencing was correlated with hypermethylation of the MEG3-differentially regulated region (DMR) in liver cancer cell lines and tumor tissues from patients. Experimental rescue of miR-493-5p promoted an anti-cancer response by hindering hepatocellular carcinoma (HCC) cell growth in vitro and tumor progression in vivo. We found that miR-493-5p mediated part of its tumor-suppressor activity by abrogating overexpression of insulin-like growth factor 2 (IGF2) and the IGF2-derived intronic oncomir miR-483-3p in HCC cells characterized by IGF2 loss of imprinting (LOI). In summary, this study describes an unknown miRNA-dependent regulatory mechanism between two distinct imprinted loci and a possible therapeutic window for liver cancer patients exhibiting IGF2-miR-483 LOI and amplification.
2018-12-05 | GSE123314 | GEO
Project description:Purpose: The 10x Genomics Visium platform allows us to define the spatial topography of gene expression and provides detailed molecular maps that overcome limitations associated with sn/scRNA-seq and microscopy-based spatial transcriptomics methods. The goals of this study are to compare and identify unique transcriptome profiling (RNA-seq) signature between unfavorable and favorable Wilms Tumors and against human fetal kidney. Methods: Human fetal kidney and Wilms tumor spatial topography of gene expression were generated using the 10X Visium platform Results: Using an optimized data analysis workflow, we mapped the reads to the hg38 genome build and grouped the spots into 9 clusters based on gene expression profiles. Conclusion: Our study represents the first implement of Visium technology in human fetal kidney and Wilms Tumor tissue, providing a number of important functional insights about the spatial and molecular definitions of cell populations across human fetal kidney and different subtypes of Wilms Tumor through analyzing gene expression within the intact spatial organization of the human samples.
2023-07-01 | GSE178349 | GEO
Project description:Precise regulation of transduction signaling pathways genes is crucial for correct differentiation of kidney cells and perturbation may lead to tumor onset. Wilms tumors (WT), or nephroblastoma, originates from the metanephric blastema cells, which were unable to complete the differentiation, resulting in a triphasic tumor composed by distinct cell types, blastemal, epithelial and stromal, where the former harbor molecular characteristics similar to cells of the earliest stages of kidney development. In this study, to identify key early events involved in the disruption of correct cell signaling during kidney differentiation that can drive WT, we developed a cDNA platform containing genes from signaling transduction pathways. By using bioinformatics tools, we defined high conserved regions between human and mouse orthologous genes and assessed the gene modulation in blastemal cells captured from WT and differentiated kidneys (DK) in human and from four temporal stages of kidney differentiation in mouse. We found 18 genes, whose transcriptional level of the earliest phases of blastemal cell differentiation was recapitulated in WT. PAX2, FZD10, SHPK, WNT5B, FZD2, CRABP2, FRZB, GRK7, TESK1, HDGF and IGF2 were up- and MAPK9, PIK3CA, FRAT2, ITPR3, CDH6, HIPK1 and TIMP3 were down-regulated in WT respectively. Hierarchical clustering based on the expression of this gene set grouped DK from both species, human and mouse, and discriminated them from fetal kidney and WT in human, and the earliest kidney stages in mouse, validating the model proposed by this study and reveling a transduction signaling signature of WT. High robustness of this data was detected since expression level was tested by quantitative RT-PCR in the initial and independent sample set, with 75 and 56% of agreement. Agreement of 62% was also observed in protein level assessing blastemal component of an independent group of 137 WT. Protein expression of CRABP2, IGF2, GRK7, TESK1, HDGF, WNT5B, FZD2 and TIMP3 was also characterized in human fetal kidneys revealing interesting aspects of kidney differentiation. This study identified key genes modulated during kidney differentiation which may play a determinant role for WT onset. As far as we know, FZD10, FRZB, HDGF, MAPK9, FRAT2, SHPK, WNT5B, GRK7, TESK1, HDGF, PIK3CA, ITPR3, HIPK1 and TIMP3 were not previously associated to WT.
2011-12-07 | GSE25965 | GEO
Project description:The global gene expression pattern of Wilms tumors in comparison with clear cell sarcoma of the kidney (CCSK) and non-neoplastic fetal and adult kidneys.
2016-02-04 | GSE73209 | GEO
Project description:Precise regulation of transduction signaling pathways genes is crucial for correct differentiation of kidney cells and perturbation may lead to tumor onset. Wilms tumors (WT), or nephroblastoma, originates from the metanephric blastema cells, which were unable to complete the differentiation, resulting in a triphasic tumor composed by distinct cell types, blastemal, epithelial and stromal, where the former harbor molecular characteristics similar to cells of the earliest stages of kidney development. In this study, to identify key early events involved in the disruption of correct cell signaling during kidney differentiation that can drive WT, we developed a cDNA platform containing genes from signaling transduction pathways. By using bioinformatics tools, we defined high conserved regions between human and mouse orthologous genes and assessed the gene modulation in blastemal cells captured from WT and differentiated kidneys (DK) in human and from four temporal stages of kidney differentiation in mouse. We found 18 genes, whose transcriptional level of the earliest phases of blastemal cell differentiation was recapitulated in WT. PAX2, FZD10, SHPK, WNT5B, FZD2, CRABP2, FRZB, GRK7, TESK1, HDGF and IGF2 were up- and MAPK9, PIK3CA, FRAT2, ITPR3, CDH6, HIPK1 and TIMP3 were down-regulated in WT respectively. Hierarchical clustering based on the expression of this gene set grouped DK from both species, human and mouse, and discriminated them from fetal kidney and WT in human, and the earliest kidney stages in mouse, validating the model proposed by this study and reveling a transduction signaling signature of WT. High robustness of this data was detected since expression level was tested by quantitative RT-PCR in the initial and independent sample set, with 75 and 56% of agreement. Agreement of 62% was also observed in protein level assessing blastemal component of an independent group of 137 WT. Protein expression of CRABP2, IGF2, GRK7, TESK1, HDGF, WNT5B, FZD2 and TIMP3 was also characterized in human fetal kidneys revealing interesting aspects of kidney differentiation. This study identified key genes modulated during kidney differentiation which may play a determinant role for WT onset. As far as we know, FZD10, FRZB, HDGF, MAPK9, FRAT2, SHPK, WNT5B, GRK7, TESK1, HDGF, PIK3CA, ITPR3, HIPK1 and TIMP3 were not previously associated to WT. The strong connection between nephrogenesis and WT highlights the importance of a detailed characterization of modulated genes belonged to signal transduction. Identification of gene expression involved in kidney differentiation arresting might be imperative to point out early alterations that drive WT onset and consequently are potential candidate as molecular marker. Here, we characterized expression pattern of genes belonged to transduction signaling pathways in blastemal cells during kidney development stages in mouse and WT in human. For that, we established a model of inter- and intra-specific hybridization to assess gene expression modulation to identify key events that drive WT onset. Dye-swap was performed for each sample as control for dye bias and used as replicate. In total, 24 frozen favorable histology WT and differentiated kidney samples were laser microdisscted for blastemal cells. Three kidneys from CD1 lineage from Mus Musculus were isolated from embryos (E) and postnatal animals (P) at ages E15.5, E17.5, P1.5 and P7.5 for laser microdissection of the blastemal cells in all stages of kidney differentiation. NA were purified with PicoPure™ RNA Isolation kit (Arcturus Engineering #KT0204) and treated with RNase-Free DNase Set (Qiagen #79254; Qiagen-Germantown MD USA).
2011-12-07 | E-GEOD-25965 | biostudies-arrayexpress
Project description: Not available
| S-EPMC5560097 | biostudies-literature
Project description:Colorectal cancer is a prevalent disease that is the third most common cause of cancer-associated death globally. The genetic mechanisms underlying tumor aggressiveness in colorectal cancer require further elucidation. Taking advantage of a large panel of human metastatic colorectal cancer xenografts and matched stem-like cell cultures (m-colospheres), we show here that overexpression of miRNA-483-3p, encoded by a frequently amplified gene locus encompassing IGF2, confers an aggressive phenotype. Following ectopic overexpression of miRNA-483-3p, m-colospheres displayed (i) increased proliferative response to exogenous EGFR family ligands EGF and neuregulin 1; (ii) increased spontaneous and growth factor-induced invasiveness and epithelial-mesenchymal transition (EMT); and (iii) enhanced stem-cell frequency and resistance to differentiation. Transcriptomic analyses and functional validation found that miRNA-483-3p directly targets NDRG1, a known metastasis suppressor responsible for downregulation of the EGFR family. As a result, induced or endogenous miRNA-483-3p overexpression associated with stimulation of the signaling pathway triggered by ERBB3, including AKT and GSK3β, which is responsible for EMT transcription factor activation. Consistently, treatment of miRNA-483-3p-overexpressing m-colospheres with selective ERBB3 antibodies counteracted their proliferative and invasive phenotype. The pro-malignant role of miRNA-483-3p was further corroborated by analysis of human colorectal tumors, where miRNA-483-3p expression levels directly correlated with expression of EMT transcription factors and poor prognosis, and downregulation of miRNA-483-3p, which prevented invasion of tumors formed by m-colosphere transplantation. These results unveil a previously unrecognized link between miRNA-483-3p, NDRG1, and ERBB3-AKT signaling, which can directly support colorectal cancer invasion and is amenable to therapeutic targeting.
2023-03-13 | GSE209535 | GEO