Multi-faceted epigenetic dysregulation of gene expression promotes esophageal squamous cell carcinoma.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32699215.
- Also identified by DOI 10.1038/s41467-020-17227-z and PMC identifier 7376194.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Epigenetic landscapes can shape physiologic and disease phenotypes. We used integrative, high resolution multi-omics methods to delineate the methylome landscape and characterize the oncogenic drivers of esophageal squamous cell carcinoma (ESCC). We found 98% of CpGs are hypomethylated across the ESCC genome. Hypo-methylated regions are enriched in areas with heterochromatin binding markers (H3K9me3, H3K27me3), while hyper-methylated regions are enriched in polycomb repressive complex (EZH2/SUZ12) recognizing regions. Altered methylation in promoters, enhancers, and gene bodies, as well as in polycomb repressive complex occupancy and CTCF binding sites are associated with cancer-specific gene dysregulation. Epigenetic-mediated activation of non-canonical WNT/β-catenin/MMP signaling and a YY1/lncRNA ESCCAL-1/ribosomal protein network are uncovered and validated as potential novel ESCC driver alterations. This study advances our understanding of how epigenetic landscapes shape cancer pathogenesis and provides a resource for biomarker and target discovery.
Medical subject headings
- Biomarkers, Tumor
- Epigenesis, Genetic
- Esophageal Neoplasms
- Esophageal Squamous Cell Carcinoma
- Gene Expression Regulation, Neoplastic