論文 - 詳細
| RRC ID | 58683 |
|---|---|
| 著者 | Asano N, Takeshima H, Yamashita S, Takamatsu H, Hattori N, Kubo T, Yoshida A, Kobayashi E, Nakayama R, Matsumoto M, Nakamura M, Ichikawa H, Kawai A, Kondo T, Ushijima T. |
| タイトル | Epigenetic reprogramming underlies efficacy of DNA demethylation therapy in osteosarcomas. |
| ジャーナル | Sci Rep |
| Abstract |
Osteosarcoma (OS) patients with metastasis or recurrent tumors still suffer from poor prognosis. Studies have indicated the efficacy of DNA demethylation therapy for OS, but the underlying mechanism is still unclear. Here, we aimed to clarify the mechanism of how epigenetic therapy has therapeutic efficacy in OS. Treatment of four OS cell lines with a DNA demethylating agent, 5-aza-2'-deoxycytidine (5-aza-dC) treatment, markedly suppressed their growth, and in vivo efficacy was further confirmed using two OS xenografts. Genome-wide DNA methylation analysis showed that 10 of 28 primary OS had large numbers of methylated CpG islands while the remaining 18 OS did not, clustering together with normal tissue samples and Ewing sarcoma samples. Among the genes aberrantly methylated in primary OS, genes involved in skeletal system morphogenesis were present. Searching for methylation-silenced genes by expression microarray screening of two OS cell lines after 5-aza-dC treatment revealed that multiple tumor-suppressor and osteo/chondrogenesis-related genes were re-activated by 5-aza-dC treatment of OS cells. Simultaneous activation of multiple genes related to osteogenesis and cell proliferation, namely epigenetic reprogramming, was considered to underlie the efficacy of DNA demethylation therapy in OS. |
| 巻・号 | 9(1) |
| ページ | 20360 |
| 公開日 | 2019-12-30 |
| DOI | 10.1038/s41598-019-56883-0 |
| PII | 10.1038/s41598-019-56883-0 |
| PMID | 31889115 |
| PMC | PMC6937291 |
| MeSH | Antineoplastic Agents / pharmacology* Antineoplastic Agents / therapeutic use Bone Neoplasms / drug therapy Bone Neoplasms / genetics* Bone Neoplasms / metabolism Bone Neoplasms / pathology Cellular Reprogramming / drug effects* Cellular Reprogramming / genetics* DNA Methylation / drug effects* Epigenesis, Genetic / drug effects* Gene Expression Profiling Gene Expression Regulation, Neoplastic / drug effects Genome-Wide Association Study Humans Osteogenesis / genetics Osteosarcoma / drug therapy Osteosarcoma / genetics* Osteosarcoma / metabolism Osteosarcoma / pathology |
| IF | 3.998 |
| 引用数 | 1 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HOS(RCB0992) MG-63(RCB1890) 143B/TK^(-)neo^(R)(RCB0701) Saos-2(RCB0428) |