Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA211221 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Vesicular genes are crucial to the development of colorectal cancer. Understanding the molecular pathways behind colorectal carcinogenesis and identifying possible treatment targets can be accomplished by analyzing alterations in vesicle genes at multi-omics. Studies on the overall alteration of vesicle genes in colorectal cancer are still lacking, nevertheless. In order to identify a potential association between vesicle genetic alterations and CRC progression, we analyzed molecular alterations in CRC vesicle genes at eight levels in this study, including mRNA, protein, and epigenetic levels. We also analyzed CRC overall survival related genes that were obtained from public database. The analysis of the proteins, chromatin structural variants (SVs), DNA methylation, chromatin accessibility, phosphorylation, ubiquitination, and malonylation of our collected CRC tissues in combination with the RNA-seq data from the TCGA database revealed the presence of multiple levels of alterations in CRC vesicle genes. We progressively examined the alterations of vesicle genes in mRNA and protein levels in CRC and discovered the hub genes COL5A1 and HSPA8. Further investigation identified the probable essential transcription factors YY1, CDX2, and CBX3. This study contributes to a thorough knowledge of the connection between vesicle genes alterations in multiple level and the development of CRC and offers a theoretical framework for the identification of novel treatment targets.
2024-05-23 | PXD036533 | Pride
Project description:Colorectal tumorigenesis proceedes through well defined clinical stages assoicated with charateristic mutations. Besides genetic alterations, epi-driver genes that are aberrantly expressed in cancers in a fashion that confers a seletive growth advantage can also contribute to tumor evolution. To gain a global view of methylation patterns in normal and maliganant colorectal epithelia, we performed genome-wide DNA methylation analysis on DNAs from 48 fresh frozen CRC samples at different stages of CRC progression. We used IlluminaHumanMethylation450 Beadchip to get a broad view of genome-wide DNA methylationdata during CRC progression and identified significantly differentially methylated genes during CRC progression
2016-05-13 | GSE77954 | GEO
Project description:Colorectal tumorigenesis proceedes through well defined clinical stages assoicated with charateristic mutations. Besides genetic alterations, epi-driver genes that are aberrantly expressed in cancers in a fashion that confers a seletive growth advantage can also contribute to tumor evolution. To gain a global view of methylation patterns in normal and maliganant colorectal epithelia, we performed genome-wide DNA methylation analysis on DNAs from 48 fresh frozen CRC samples at different stages of CRC progression. We used IlluminaHumanMethylation450 Beadchip to get a broad view of genome-wide DNA methylationdata during CRC progression and identified significantly differentially methylated genes during CRC progression A total of 48 macro-dissected tissues including normal colon tissue, adenomas, carcinomas and metastases were collected by the Department of Pathology at the University of Virginia under the supervision of an experienced pathologist. DNA was extracted and run on IlluminaHumanMethylation450 Beadchip by Expression Analyisis.
2016-05-13 | E-GEOD-77954 | biostudies-arrayexpress
Project description:<p>Metabolic lesions with pleiotropic effects on epigenetic regulation and other cellular processes are widely implicated in cancer, yet their oncogenic mechanisms remain poorly understood. Succinate dehydrogenase (SDH) deficiency causes a subset of gastrointestinal stromal tumors (GISTs) with DNA hyper-methylation. Here we associate this hyper-methylation with changes in chromosome topology that activate oncogenic programs. To investigate epigenetic alterations in this disease, we systematically mapped DNA methylation, CTCF insulators, enhancers and chromosome topology in KIT-mutant, PDGFRA-mutant and SDH-deficient GISTs. Although these respective subtypes share similar enhancer landscapes, we identified hundreds of putative insulators where DNA methylation replaced CTCF binding in SDH-deficient GISTs. We focused on disrupted insulators that partitions super-enhancers from FGF3, FGF4 and the KIT oncogene. Recurrent loss of this insulator alters locus topology in SDH-deficient GISTs, allowing aberrant physical interaction between enhancers and oncogenes. CRISPR-mediated excision of the corresponding CTCF motif in an SDH-intact model disrupted the boundary and up-regulated FGFs and KIT expression. Our findings reveal how a metabolic lesion destabilizes chromatin structure to facilitate the initiation and selection of epigenetic alterations that drive oncogenic programs in the absence of canonical mutations.</p>
| phs001906 | dbGaP
Project description:DNA methylation is a key mechanism in transcription regulation, and aberrant methylation is a common and important mechanism in tumor initiation, maintenance, and progression. To find genes that are aberrantly regulated by altered methylation in horse sarcoids, we used reduced representation bisulfite sequencing (RRBS) accompanied by RNA sequencing (RNA-Seq) for methylome (whole genome DNA methylation sequencing) and transcriptome profiling, respectively. We found that the DNA methylation level was generally lower in lesion samples than in controls. In the analyzed samples, a total of 14,692 differentially methylated sites (DMSs) in the context of CpG (where cytosine and guanine are separated by a phosphate), and 11,712 differentially expressed genes (DEGs) were identified. The integration of the methylome and transcriptome data suggests that aberrant DNA methylation may be involved in the deregulation of expression of the 493 genes in equine sarcoid. Furthermore, enrichment analysis of the genes demonstrated the activation of multiple molecular pathways related to extracellular matrix (ECM), oxidative phosphorylation (OXPHOS), immune response, and disease processes that can be related to tumor progression. The results provide further insight into the epigenetic alterations in equine sarcoids and provide a valuable resource for follow-up studies to identify biomarkers for predicting susceptibility to this common condition in horses.
2023-07-03 | GSE208778 | GEO
Project description:Global methylation analysis of development and progression of colorectal carcinoma
| PRJNA312196 | ENA
Project description:The minichromosome maintenance complex (MCM) DNA helicase is an important replicative factor during DNA replication. The proper chromatin loading of MCM is a key step to ensure replication initiation during G1/S phase. Because replication initiation is regulated by multiple biological cues, additional changes to MCM may provide deeper understanding towards this event. Here, we uncover that the histidine methyltransferase SETD3 promotes DNA replication in an enzymatic activity dependent manner. Nascent-strand sequencing (NS-seq) shows that SETD3 regulates replication initiation, as depletion of SETD3 attenuates early replication origins firing. Mechanistically, biochemical experiments reveal that SETD3 binds MCM mainly during G1/S phase, which is required for CDT1-mediated chromatin loading of MCM. The MCM loading relies on the histidine-459 methylation (H459me) on MCM7 that is catalyzed by SETD3. Impairment of H459 methylation attenuates DNA synthesis and chromatin loading of MCM. Furthermore, we show that CDK2 phosphorylates SETD3 at Serine-21 during the G1/S phase, which is required for DNA replication and cell cycle progression. These findings demonstrate a novel mechanism by which SETD3 methylates MCM to regulate replication initiation.
2024-03-12 | GSE243937 | GEO
Project description:Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the severe human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of severe PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH in its later stage, which may differ from the earlier stage of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH. Global profiles were determined in human lung tissue and compared across 11 normal and 12 severe pulmonary arterial hypertension patients. Using a combination of microarray and high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the severe human PAH lung.
2014-11-14 | E-GEOD-53408 | biostudies-arrayexpress
Project description:Epigenetic change of genes expression, including hypomethylation-linked activation of oncogenes and hypermethylation-associated inactivation of tumor suppressor genes, can affect almost all the cellular signaling pathways that participate in cancer initiation and progression. Unlike genetic alterations, epigenetic changes are potentially reversible, making them attractive and promising targets for therapeutic intervention. Studies indicated that abnormal DNA methylation is involved in dysregulation of cell cycle, apoptosis, proliferation and differentiation of osteosarcoma. However, epigenetic mechanisms of osteosarcoma metastasis remain largely unknown.
2015-08-25 | GSE55961 | GEO
Project description:Epigenetic change of genes expression, including hypomethylation-linked activation of oncogenes and hypermethylation-associated inactivation of tumor suppressor genes, can affect almost all the cellular signaling pathways that participate in cancer initiation and progression. Unlike genetic alterations, epigenetic changes are potentially reversible, making them attractive and promising targets for therapeutic intervention. Studies indicated that abnormal DNA methylation is involved in dysregulation of cell cycle, apoptosis, proliferation and differentiation of osteosarcoma. However, epigenetic mechanisms of osteosarcoma metastasis remain largely unknown. MeDIP chips are performed in ZOS and ZOSM—two syngeneic primary human osteosarcoma cell lines with low and high metastatic potential which are established in our lab
2015-08-25 | E-GEOD-55961 | biostudies-arrayexpress