An Integrated Epigenome and Transcriptome Analysis to Clarify the Effect of Epigenetic Inhibitors on GIST
| Autor: | M Toyota, Taku Harada, Hironori Aoki, Hiroshi Kitajima, Gota Sudo, Masahiro Kai, Takeshi Niinuma, Hiroshi Nakase, Tamotsu Sugai, Eiichiro Yamamoto, Reo Maruyama, Hiromu Suzuki, Ayano Yoshido, Kazuya Ishiguro |
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| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Gastrointestinal Stromal Tumors medicine.drug_class Gene Expression Epigenesis Genetic Histones Transcriptome Epigenome Cell Line Tumor medicine Humans Gene Silencing Epigenetics neoplasms Gastrointestinal Neoplasms GiST biology Histone deacetylase inhibitor General Medicine DNA Methylation digestive system diseases Histone Deacetylase Inhibitors Histone Oncology DNA methylation biology.protein Cancer research H3K4me3 |
| Zdroj: | Anticancer Research. 41:2817-2828 |
| ISSN: | 1791-7530 0250-7005 |
| Popis: | Background/aim Epigenetic alterations play an important role in the pathogenesis of gastrointestinal stromal tumors (GISTs). To obtain further insight into the GIST epigenome, we analyzed genome-wide histone modification and DNA methylation in GIST cells. Materials and methods To reverse epigenetic silencing, GIST-T1 cells were treated with a DNA methyltransferase inhibitor and a histone deacetylase inhibitor, and subsequently H3K4me3 levels, the DNA methylome, and the transcriptome were analyzed. Results Treatment with epigenetic inhibitors not only up-regulated genes with DNA methylation, but also genes related to interferon signaling. ChIP-seq analysis revealed that drug treatment up-regulated H3K4me3 levels in retrotransposons, including endogenous retroviruses (ERV). Finally, utilizing the omics data, we found that hypermethylation of MEG3 is a frequent event and an indicator of poorer prognosis in GIST patients. Conclusion Epigenetic inhibitors may activate interferon signaling via viral mimicry in GIST cells. Moreover, epigenome data could be a useful resource to identify novel GIST-related genes. |
| Databáze: | OpenAIRE |
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