Project description:Aberrant DNA methylation is an epigenetic hallmark of cancer, known to play an essential role in cancer initiation, progression and drug resistance. Traditional analyses focus on mean methylation that measures the aggregated signal across a group of cells and neglect intra-sample heterogeneity. Sequencing-based techniques such as whole genome bisulfite sequencing (WGBS) are now widely used to measure DNA methylation on each read at single-nucleotide resolution. A single read fragment stems from a single chromosome of a single cell and represents a DNA methylation haplotype (mHap). In this study, we have profiled 110 fresh frozen tumor samples that cover 11 most common solid cancer types using WGBS and constructed a comprehensive DNA methylation haplotype map.
Project description:We report a map of H3K4me3 - an activiting expression histone modification in C6 rat glioma cells. The data was obtained using whole genome high throughput technology. The sequencing was performed on Solid 5500xl platform.
Project description:We report a map of H3K4me3 - an activiting expression histone modification in C6 rat glioma cells. The data was obtained using whole genome high throughput technology. The sequencing was performed on Solid 5500xl platform. Examination of H3K4me3 histone modification in C6 rat glioma cell line
Project description:Metastasis is the main cause of cancer-related deaths, yet the underlying mechanisms remain elusive. Using clear cell renal cell carcinoma (ccRCC), a tumor type with frequent lung metastases, we conducted an in vivo genome-wide CRISPR-Cas9 screen and identified HLF as a potent suppressor of lung metastasis. While HLF translocation is known as an oncogenic event in leukemia, its role in solid cancers remains unclear. Our study revealed that HLF depletion enhanced ccRCC migration and lung metastasis, whereas HLF overexpression abrogated these effects. This finding extended to multiple solid tumor types. In ccRCC patients, HLF expression was reduced at metastatic sites and associated with epigenetic silencing. HLF levels negatively correlated with migration potential in collagen. Mechanistically, HLF regulated leupaxin expression, affecting the integration of collagen stiffness and the actin cytoskeleton through paxillin, thereby repressing cancer cell migration and lung metastasis. These data indicate that HLF influences lung metastasis through cell-collagen interactions in solid tumors.
Project description:Epigenetic therapy is emerging as a potential therapy for solid tumors. To investigate its mechanism of action, we performed integrative expression and methylation analysis of 63 cancer cell lines (breast, colorectal, and ovarian) after treatment with the DNA methyltransferase inhibitor 5-azacitidine (AZA). Gene Set Enrichment Analysis demonstrated significant enrichment for immunomodulatory pathways in all three cancers (14.4-31.3%) including interferon signaling, antigen processing and presentation, and cytokines/chemokines. Strong upregulation of cancer testis antigens was also observed. An AZA IMmune gene set (AIMs) derived from the union of these immunomodulatory pathway genes classified primary tumors from all three types, into “high” and “low” AIM gene expression subsets in tumor expression data from both TCGA and GEO (GSE42284, GSE10893, and GSE26712 for the colon, breast, and ovarian samples, respectively). Samples from selected patient biopsies showed upregulation of AIM genes after treatment with epigenetic therapy. These results point to a broad immune stimulatory role for DNA demethylating drugs in multiple cancers. A total of 338 samples were analyzed.