Loss of SUV420H2-dependent chromatin compaction drives right-sided colon cancer progression
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PROVIDER: PRJNA898311 | ENA |
REPOSITORIES: ENA
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Project description:Loss of SUV420H2-dependent chromatin compaction drives right-sided colon cancer progression [CGH]
| PRJNA898317 | ENA
Project description:Loss of SUV420H2-dependent chromatin compaction drives right-sided colon cancer progression [RNA-seq]
| PRJNA898316 | ENA
Project description:Purpose: Over the past few years, the distinction between left- and right-sided colon cancer has been brought into focus. Right-sided tumor location was associated with an inferior overall survival and progression-free survival. We aimed to perform a detailed analysis of the diversity in exosomes between left- and right-sided colon cancer using quantitative proteomics. Experimental Design: We isolated exosomes from left- and right-sided colon cancer patients and healthy volunteers and treated colorectal cancer cell line with serum-derived exosomes. Then we performed quantitative proteomics analysis of the serum-derived exosomes and cell line treated with exosomes, respectively. Results: The expression profile of the serum exosome proteome in patients with right-sided colon cancer is different from patients with left-sided colon cancer. Serum-derived exosomes of right-sided colon cancer promote metastasis via up-regulation of extracellular matrix-related proteins, especially proteoglycans like SPARC and glycoprotein like LRG1. Exosomal SPARC and LRG1 were closely correlated with progression-free survival. Conclusions: Proteomic analysis identified different exosomal protein profiling between left- and right-sided colon cancer. Serum-derived exosomes of right-sided colon cancer promote metastasis via overexpression of SPARC and LRG1.
2019-11-25 | PXD012304 | Pride
Project description:In our study, we obtained paired normal left-sided and right-sided colon mucosa tissues by colonoscopy, and 9,642 individual cells were analyzed by single-cell RNA-seq, which aims to explore the differennces of cell component between the left and the right colon.
2024-06-10 | GSE176499 | GEO
Project description:Epigenetic processes regulating gene expression contribute markedly to epithelial cell plasticity in colorectal carcinogenesis. The lysine methyltransferase SUV420H2 comprises an important regulator of epithelial plasticity and is primarily responsible for trimethylation of H4K20 (H4K20me3). Loss of H4K20me3 has been suggested as a hallmark of human cancer due to its interaction with DNMT1. However, the role of Suv4-20h2 in colorectal cancer is unknown.
2022-11-09 | GSE217265 | GEO
Project description:Epigenetic processes regulating gene expression contribute markedly to epithelial cell plasticity in colorectal carcinogenesis. The lysine methyltransferase SUV420H2 comprises an important regulator of epithelial plasticity and is primarily responsible for trimethylation of H4K20 (H4K20me3). Loss of H4K20me3 has been suggested as a hallmark of human cancer due to its interaction with DNMT1. However, the role of Suv4-20h2 in colorectal cancer is unknown.
2022-11-09 | GSE217266 | GEO
Project description:Background & aimsEpigenetic processes regulating gene expression contribute markedly to epithelial cell plasticity in colorectal carcinogenesis. The lysine methyltransferase SUV420H2 comprises an important regulator of epithelial plasticity and is primarily responsible for trimethylation of H4K20 (H4K20me3). Loss of H4K20me3 has been suggested as a hallmark of human cancer due to its interaction with DNMT1. However, the role of Suv4-20h2 in colorectal cancer is unknown.MethodsWe examined the alterations in histone modifications in patient-derived colorectal cancer organoids. Patient-derived colorectal cancer organoids and mouse intestinal organoids were genetically manipulated for functional studies in patient-derived xenograft and orthotopic transplantation. Gene expression profiling, micrococcal nuclease assay, and chromatin immunoprecipitation were performed to understand epigenetic regulation of chromatin states and gene expression in patient-derived and mouse intestinal organoids.ResultsWe found that reduced H4K20me3 levels occurred predominantly in right-sided patient-derived colorectal cancer organoids, which were associated with increased chromatin accessibility. Re-compaction of chromatin by methylstat, a histone demethylase inhibitor, resulted in reduced growth selectively in subcutaneously grown tumors derived from right-sided cancers. Using mouse intestinal organoids, we confirmed that Suv4-20h2-mediated H4K20me3 is required for maintaining heterochromatin compaction and to prevent R-loop formation. Cross-species comparison of Suv4-20h2-depleted murine organoids with right-sided colorectal cancer organoids revealed a large overlap of gene signatures involved in chromatin silencing, DNA methylation, and stemness/Wnt signaling.ConclusionsLoss of Suv4-20h2-mediated H4K20me3 drives right-sided colorectal tumorigenesis through an epigenetically controlled mechanism of chromatin compaction. Our findings unravel a conceptually novel approach for subtype-specific therapy of this aggressive form of colorectal cancer.
| S-EPMC9889219 | biostudies-literature
Project description:Single-Cell Transcriptome Analysis Reveals Differential Signatures of Human Left-Sided and Right-Sided Colon
| PRJNA736439 | ENA
Project description:Colorectal cancers (CRCs) exhibit differences in incidence, pathogenesis, molecular pathways and outcome depending on the location of the tumor. The transcriptomes of 27,927 single human CRC cells, from three left-sided and three right-sided CRC patients were profiled by scRNA-seq. Right-sided CRC harbors a significant proportion of exhausted CD8 T cells of a highly migratory nature. One cluster of cells from left-sided CRC exhibiting states preceding exhaustion and a high ratio of “pre-exhausted” to exhausted T cells were favorable prognostic markers. Notably, we identified a novel RBP4+ NTS+ subpopulation of cancer cells that exclusively expands in left-sided CRC. Tregs from left-sided CRC showed higher levels of immunotherapy-related genes than those from right-sided CRC, indicating that left-sided CRC may have increased responsiveness to immunotherapy. Antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) induced by M2-like macrophages were more pronounced in left-sided CRC and correlated with a good prognosis in CRC.
2021-11-15 | GSE188711 | GEO
Project description:Purpose: Over the past few years, the distinction between left- and right-sided colon cancer has been brought into focus. Right-sided tumor location was associated with an inferior overall survival and progression-free survival. We aimed to perform a detailed analysis of the diversity in exosomes between left- and right-sided colon cancer using quantitative proteomics. Experimental Design: We isolated exosomes from left- and right-sided colon cancer patients and healthy volunteers and treated colorectal cancer cell line with serum-derived exosomes. Then we performed quantitative proteomics analysis of the serum-derived exosomes and cell line treated with exosomes, respectively. Results: The expression profile of the serum exosome proteome in patients with right-sided colon cancer is different from patients with left-sided colon cancer. Serum-derived exosomes of right-sided colon cancer promote metastasis via up-regulation of extracellular matrix-related proteins, especially proteoglycans like SPARC and glycoprotein like LRG1. Exosomal SPARC and LRG1 were closely correlated with progression-free survival. Conclusions: Proteomic analysis identified different exosomal protein profiling between left- and right-sided colon cancer. Serum-derived exosomes of right-sided colon cancer promote metastasis via overexpression of SPARC and LRG1.
2019-11-25 | PXD012283 | Pride