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Genome-wide profiling of DNA methylation and gene expression in radiation-resistant esophageal cancer cells
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| L-R Zhou, L. Wang, Z-C Tao, M. Cheng, J. Gao, L-T Qian |
| Department of Radiation Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230031, China , money2004@sina.com |
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Abstract: (455 Views) |
Background: While there have been marked improvements in radiotherapeutic techniques in recent years, the emergence of radioresistance remains a pressing challenge to the clinical treatment of esophageal squamous cell carcinoma (ESCC). Altered DNA methylation is believed to play a role in the etiology of such resistance. This study was designed to explore patterns of altered genome-wide gene expression and DNA methylation patterns in radioresistant ESCC cells (TE1-res) in an effort to provide a foundation for the future study of the molecular drivers that underlie this form of therapeutic resistance. Materials and Methods: A microarray-based approach was used to conduct genome-wide DNA methylation and gene expression analyses using matched radioresistant and radioresistant ESCC cells. The mechanistic basis for ESCC cell radioresistance was then further examined through functional enrichment and protein-protein interaction analyses. Results: Relative to parental TE1 cells, TE1-res cells exhibited marked changes in their DNA methylation profiles, with the disproportional distribution of differentially methylated CpG sites (dmCpGs) in CpG islands and shore regions. Ontological analyses revealed that genes that were differentially expressed and methylated were enriched in the Ras protein signal transduction, regulation of DNA damage response, and angiogenesis pathways. Protein-protein interaction analyses further suggested that ACTL8, M-RAS, TRIB2, GATA5, ERBB4, FN1, DIRAS1, BTK, ROR1, and NPR3 may serve as hub proteins within TE1-res cells. Conclusions: These analyses revealed a significant association between DNA methylation and TE1-res cell radioresistance, highlighting several candidate genes and pathways that may be amenable to clinical targeting in an effort to increase the radiosensitivity of these ESCC cells. |
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| Keywords: Esophageal cancer cell line, Radiation tolerance, Gene microarray, DNA methylation. |
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Full-Text [PDF 1057 kb]
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Type of Study: Original Research |
Subject:
Radiation Biology
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