RNA-sequencing of renal cells from Setd2-wildtype PKD and Setd2-knlckout ccRCC mice.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA913096 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22997900_1.fastq.gz | Fastqsanger.gz | |||
| SRR22997900_2.fastq.gz | Fastqsanger.gz | |||
| SRR22997901_1.fastq.gz | Fastqsanger.gz | |||
| SRR22997901_2.fastq.gz | Fastqsanger.gz | |||
| SRR22997902_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 20 |
Similar Datasets
Project description:To explore potential role of SETD2 in PKD-ccRCC transition in vivo, we generated a PKD mouse model by overexpressing oncogene c-MYC under the control of the Ksp promoter (KM mice), and knockout Setd2 gene using the same Ksp promoter in this PKD mice (KMs mice) to establish a ccRCC mouse model. To further characterize biological responses trigered by SETD2 deletion during PKD-ccRCC transition at the mRNA level, we next conducted global transcriptomics studies.
2022-12-26 | GSE221136 | GEO
Project description:Patients with polycystic kidney disease (PKD) encounter a high risk of clear cell renal cell carcinoma (ccRCC), a malignant tumor with dysregulated lipid metabolism. SET domain–containing 2 (SETD2) has been identified as an important tumor suppressor gene in ccRCC. However, the role of SETD2 in tumorigenesis during the transition from PKD to ccRCC remains largely unexplored. Herein, we performed metabolomics, lipidomics, transcriptomics and proteomics with SETD2 loss induced PKD-ccRCC transition mouse model. To characterize biological responses triggered by SETD2 deletion during PKD-ccRCC transition at the protein level, we conducted global proteomics studies.
2023-10-31 | PXD038966 | Pride
Project description:SETD2, a H3K36 trimethyltransferase, is frequently mutated in human cancers with the highest prevalence (13%) in clear cell renal cell carcinoma (ccRCC). Genomic profiling of primary ccRCC tumors reveals a positive correlation between SETD2 mutations and metastasis. However, whether and how SETD2-loss promotes metastasis remains unclear. Here, we detected SETD2 mutations in 24 of 51 (47%) metastatic ccRCC tumors. Using SETD2-mutant metastatic ccRCC patient-derived cell line and xenograft models, we showed that H3K36me3 restoration greatly reduced distant metastases of ccRCC in mice. An integrated ATAC-seq, ChIP-seq, and transcriptome analysis concluded a tumor suppressor model in which loss of SETD2-mediated H3K36me3 activates enhancers to drive oncogenic transcription through dysregulating histone chaperone recruitment, enhancing histone exchange, and expanding chromatin accessibility. Furthermore, we uncovered mechanism-based therapeutic strategies for SETD2-deficient cancer through inhibition of histone chaperones. Overall, SETD2-loss creates a permissive epigenetic landscape for cooperating oncogenic drivers to amplify transcriptional output, providing unique therapeutic opportunities.
2021-11-15 | GSE146537 | GEO
Project description:SETD2, a H3K36 trimethyltransferase, is frequently mutated in human cancers with the highest prevalence (13%) in clear cell renal cell carcinoma (ccRCC). Genomic profiling of primary ccRCC tumors reveals a positive correlation between SETD2 mutations and metastasis. However, whether and how SETD2-loss promotes metastasis remains unclear. Here, we detected SETD2 mutations in 24 of 51 (47%) metastatic ccRCC tumors. Using SETD2-mutant metastatic ccRCC patient-derived cell line and xenograft models, we showed that H3K36me3 restoration greatly reduced distant metastases of ccRCC in mice. An integrated ATAC-seq, ChIP-seq, and transcriptome analysis concluded a tumor suppressor model in which loss of SETD2-mediated H3K36me3 activates enhancers to drive oncogenic transcription through dysregulating histone chaperone recruitment, enhancing histone exchange, and expanding chromatin accessibility. Furthermore, we uncovered mechanism-based therapeutic strategies for SETD2-deficient cancer through inhibition of histone chaperones. Overall, SETD2-loss creates a permissive epigenetic landscape for cooperating oncogenic drivers to amplify transcriptional output, providing unique therapeutic opportunities.
2021-11-15 | GSE146540 | GEO
Project description:SETD2, a H3K36 trimethyltransferase, is frequently mutated in human cancers with the highest prevalence (13%) in clear cell renal cell carcinoma (ccRCC). Genomic profiling of primary ccRCC tumors reveals a positive correlation between SETD2 mutations and metastasis. However, whether and how SETD2-loss promotes metastasis remains unclear. Here, we detected SETD2 mutations in 24 of 51 (47%) metastatic ccRCC tumors. Using SETD2-mutant metastatic ccRCC patient-derived cell line and xenograft models, we showed that H3K36me3 restoration greatly reduced distant metastases of ccRCC in mice. An integrated ATAC-seq, ChIP-seq, and transcriptome analysis concluded a tumor suppressor model in which loss of SETD2-mediated H3K36me3 activates enhancers to drive oncogenic transcription through dysregulating histone chaperone recruitment, enhancing histone exchange, and expanding chromatin accessibility. Furthermore, we uncovered mechanism-based therapeutic strategies for SETD2-deficient cancer through inhibition of histone chaperones. Overall, SETD2-loss creates a permissive epigenetic landscape for cooperating oncogenic drivers to amplify transcriptional output, providing unique therapeutic opportunities.
2021-11-15 | GSE146539 | GEO
Project description:RNA N6-methyladenosine (m6A) plays diverse roles in RNA metabolism and its deregulation contributes to tumor initiation and progression. Clear cell renal cell carcinoma (ccRCC) is characterized by near ubiquitous loss of VHL followed by mutations in epigenetic regulators PBRM1, SETD2, and BAP1. Mutations in SETD2, a histone H3 lysine 36 trimethylase (H3K36me3), are associated with reduced survival, greater metastatic propensity, and metabolic reprogramming. While m6A and H3K36me3 deregulation are separately implicated in renal tumorigenesis, H3K36me3 may participate directly in m6A targeting, but the m6A-H3K36me3 interplay has not been investigated in the context of ccRCC. Using RCC-relevant SETD2 isogenic knockout and rescue cell line models, we demonstrate a dynamic redistribution of m6A in the SETD2 depleted transcriptome, with a subset of transcripts involved in metabolic reprogramming demonstrating SETD2 dependent m6A and expression level changes. Using a panel of six histone modifications we show that m6A redistributes to regions enriched in gained active enhancers upon SETD2 inactivation. Finally, we demonstrate a reversal of transcriptomic programs involved in SETD2 loss mediated metabolic reprogramming, and reduced cell viability through pharmacological inhibition or genetic ablation of m6A writer METTL3 specific to SETD2 deficient cells. Thus, targeting m6A may represent a novel therapeutic vulnerability in SETD2 mutant ccRCC.
2025-01-17 | GSE276371 | GEO
Project description:RNA N6-methyladenosine (m6A) plays diverse roles in RNA metabolism and its deregulation contributes to tumor initiation and progression. Clear cell renal cell carcinoma (ccRCC) is characterized by near ubiquitous loss of VHL followed by mutations in epigenetic regulators PBRM1, SETD2, and BAP1. Mutations in SETD2, a histone H3 lysine 36 trimethylase (H3K36me3), are associated with reduced survival, greater metastatic propensity, and metabolic reprogramming. While m6A and H3K36me3 deregulation are separately implicated in renal tumorigenesis, H3K36me3 may participate directly in m6A targeting, but the m6A-H3K36me3 interplay has not been investigated in the context of ccRCC. Using RCC-relevant SETD2 isogenic knockout and rescue cell line models, we demonstrate a dynamic redistribution of m6A in the SETD2 depleted transcriptome, with a subset of transcripts involved in metabolic reprogramming demonstrating SETD2 dependent m6A and expression level changes. Using a panel of six histone modifications we show that m6A redistributes to regions enriched in gained active enhancers upon SETD2 inactivation. Finally, we demonstrate a reversal of transcriptomic programs involved in SETD2 loss mediated metabolic reprogramming, and reduced cell viability through pharmacological inhibition or genetic ablation of m6A writer METTL3 specific to SETD2 deficient cells. Thus, targeting m6A may represent a novel therapeutic vulnerability in SETD2 mutant ccRCC.
2025-01-17 | GSE276357 | GEO
Project description:To explore a possible role of SETD2 in kidney development and tumorigenesis in vivo, we generated Setd2-floxed mice and deleted the Setd2 gene in tubular epithelial cells using a transgenic Ksp1.3/Cre mouse line. Then, we established our own c-MYC-transgene mouse line by overexpressing the human c-MYC under the control of the Ksp promoter to generate kidney disease mouse model. To get an insight into the mechanism of how SETD2 ablation promotes ccRCC formation in a c-MYC-generated PKD model, we performed RNA-seq using the renal tubules isolated from Wild Type, Setd2-KO, MYC-OE and MYC-OE; Setd2-KO mice.
2021-03-14 | GSE168849 | GEO
Project description:SETD2, a H3K36 trimethyltransferase, is frequently mutated in human cancers with the highest prevalence (13%) in clear cell renal cell carcinoma (ccRCC). Genomic profiling of primary ccRCC tumors reveals a positive correlation between SETD2 mutations and metastasis. However, whether and how SETD2-loss promotes metastasis remains unclear. Here, we detected SETD2 mutations in 24 of 51 (47%) metastatic ccRCC tumors. Using SETD2-mutant metastatic ccRCC patient-derived cell line and xenograft models, we showed that H3K36me3 restoration greatly reduced distant metastases of ccRCC in mice. An integrated ATAC-seq, ChIP-seq, and transcriptome analysis concluded a tumor suppressor model in which loss of SETD2-mediated H3K36me3 activates enhancers to drive oncogenic transcription through dysregulating histone chaperone recruitment, enhancing histone exchange, and expanding chromatin accessibility. Furthermore, we uncovered mechanism-based therapeutic strategies for SETD2-deficient cancer through inhibition of histone chaperones. Overall, SETD2-loss creates a permissive epigenetic landscape for cooperating oncogenic drivers to amplify transcriptional output, providing unique therapeutic opportunities.
2021-11-15 | GSE146538 | GEO
Project description:SETD2, a H3K36 trimethyltransferase, is frequently mutated in human cancers with the highest prevalence (13%) in clear cell renal cell carcinoma (ccRCC). Genomic profiling of primary ccRCC tumors reveals a positive correlation between SETD2 mutations and metastasis. However, whether and how SETD2-loss promotes metastasis remains unclear. Here, we detected SETD2 mutations in 24 of 51 (47%) metastatic ccRCC tumors. Using SETD2-mutant metastatic ccRCC patient-derived cell line and xenograft models, we showed that H3K36me3 restoration greatly reduced distant metastases of ccRCC in mice. An integrated ATAC-seq, ChIP-seq, and transcriptome analysis concluded a tumor suppressor model in which loss of SETD2-mediated H3K36me3 activates enhancers to drive oncogenic transcription through dysregulating histone chaperone recruitment, enhancing histone exchange, and expanding chromatin accessibility. Furthermore, we uncovered mechanism-based therapeutic strategies for SETD2-deficient cancer through inhibition of histone chaperones. Overall, SETD2-loss creates a permissive epigenetic landscape for cooperating oncogenic drivers to amplify transcriptional output, providing unique therapeutic opportunities.
2021-11-15 | GSE146541 | GEO