Molecular pathology of SET-related histone methyltransferase in refractory cancer
Project/Area Number |
16K08647
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Human pathology
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
Akiyama Yoshimitsu 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (80262187)
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Co-Investigator(Kenkyū-buntansha) |
田中 真二 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30253420)
島田 周 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (20609705)
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Project Period (FY) |
2016-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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Keywords | エピジェネティクス / エピゲノム / ヒストン修飾 / メチル化 / 難治性消化器癌 / SETドメイン / クロマチン免疫沈降法 / 難治性癌 / ヒストンメチル化 |
Outline of Final Research Achievements |
We focused on alterations of histone methyltransferases with SET domain in refractory cancer. Overexpression of SETDB2 was detected in approximately 40% of gastric cancer (GC), and the GC patients with SETDB2 overexpression significantly showed worse prognosis. SETDB2 overexpression in GC cells accelerated cell growth and invasiveness, and suppressed the expression levels of WWOX and CADM1, tumor suppressor genes, through histone H3K9 trimethylation changes. These data suggest that SETDB2 has oncogenic roles and plays an important role in malignant progression of GC. Overexpression of PRMT6 and loss of KDM6A were detected in refractory cancer as well. Finally, we optimized the condition of chromatin immunoprecipitation assay for the primary cancer tissues.
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Academic Significance and Societal Importance of the Research Achievements |
エピゲノム研究分野において、ヒストン修飾異常の解析が進んでいる。SETDB1やEZH2などのSETドメイン含有酵素の異常が多くの癌で報告され、その阻害剤の研究が進んでいる。SETDB2に関しては全く不明であったが、本研究でSETDB2の高発現、および癌促進的が明らかになったことで、今後、この酵素に着目した治療薬の開発につながると期待できる。臨床検体におけるヒストン修飾解析は培養細胞株に比べて困難であったが、本研究でその条件設定を行い癌組織でもヒストン修飾変化を解析できるようになった。
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Report
(5 results)
Research Products
(36 results)
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[Journal Article] Loss of ARID1A induces a stemness gene ALDH1A1 expression with histone acetylation in the malignant subtype of cholangiocarcinoma.2020
Author(s)
Yoshino J, Akiyama Y, Shimada S, Ogura T, Ogawa K, Ono H, Mitsunori Y, Ban D, Kudo A, Yamaoka S, Tanabe M, Tanaka S.
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Journal Title
Carcinogenesis
Volume: in press
Pages: 0000-0000
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Upregulation of cancer-associated gene expression in activated fibroblasts in a mouse model of non-alcoholic steatohepatitis2019
Author(s)
Asakawa M, Itoh M, Suganami T, Sakai T, Kanai S, Shirakawa I, Yuan X, Hatayama T, Shimada S, Akiyama Y, Fujiu K, Inagaki Y, Manabe I, Yamaoka S, Yamada T, Tanaka S, Ogawa Y.
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Journal Title
Sci. Rep.
Volume: 9
Pages: 19601-19601
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Comprehensive molecular characterization of liver cancer and inheritance of the phenotypic traits during tumor recurrence.2019
Author(s)
Shimada S, Mogushi K, Akiyama Y, Furuyama T, Watanabe S, Ogura T, Ogawa K, Ono H, Mitsunori Y, Ban D, Kudo A, Arii S, Tanabe M, Wands JR, Tanaka S.
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Journal Title
EBioMedicine.
Volume: 40
Pages: 457-470
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A subset of diffuse-type gastric cancer is susceptible to mTOR inhibitors and checkpoint inhibitors2019
Author(s)
Fukamachi H., Kim S., K., Koh J., Lee H. S., Sasaki Y., Yamashita K., Nishikawaji T., Shimada S., Akiyama Y., Byeon S. J., Bae D. H., Okuno K., Nakagawa M., Tanioka T., Inokuchi M., Kawachi H., Tsuchiya K., Kojima K., Tokino T., Eishi Y., Kim Y. S., Kim W. H., Yuasa Y., Tanaka S.
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Journal Title
J Exp Clin Cancer Res
Volume: 38
Pages: 127-127
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Tumor suppressor functions of DAXX through histone H3.3/H3K9me3 pathway in pancreatic NETs.2018
Author(s)
Ueda H, Akiyama Y, Shimada S, Mogushi K, Serizawa M, Matsumura S, Mitsunori Y, Aihara A, Ban D, Ochiai T, Kudo A, Tanabe M, Tanaka S.
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Journal Title
Endocrine-Related Cancer
Volume: 25(6)
Pages: 619-631
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Acquired resistance with epigenetic alterations under long-term anti-angiogenic therapy for hepatocellular carcinoma.2017
Author(s)
Ohata Y, Akiyama Y, Shimada S, Mogushi K, Nakao K, Matsumura S, Aihara A, Mitsunori Y, Ban D, Ochiai T, Kudo A, Tanabe M, Tanaka S.
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Journal Title
Mol Cancer Ther.
Volume: in press
Pages: 1155-1165
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Meeting Report of the Fifth International Cancer Epigenetics Conference in Beijing, China, October 20162017
Author(s)
Gao D, Herman JG, Cui H, Jen J, Fuks F, Brock MV, Ushijima T, Croce C, Akiyama Y, Guo M.
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Journal Title
Epigenomics
Volume: 9
Pages: 937-941
DOI
Related Report
Open Access / Int'l Joint Research
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[Journal Article] ARID2 modulates DNA damage response in human hepatocellular carcinoma cells.2017
Author(s)
Oba A, Shimada S, Akiyama Y, Nishikawaji T, Mogushi K, Ito H, Matsumura S, Aihara A, Mitsunori Y, Ban D, Ochiai T, Kudo A, Asahara H, Kaida A, Miura M, Tanabe M, Tanaka S.
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Journal Title
J Hepatol.
Volume: in press
Pages: 942-951
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] プレシジョン・メディシンの外科学への応用 ゲノム医療・ゲノム編集時代におけるプレシジョン免疫複合療法.2019
Author(s)
田中 真二, 島田 周, 秋山 好光, 大庭 篤志, 渡辺 秀一, 奥野 圭祐, 水野 裕貴, 上田 浩樹, 吉野 潤, 菅原 了子, 小倉 俊郎, 小川 康介, 光法 雄介, 小野 宏晃, 伴 大輔, 工藤 篤, 大久保 憲一, 小嶋 一幸, 絹笠 祐介, 田邉 稔.
Organizer
第119回日本外科学会定期学術集会
Related Report
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[Presentation] Reduced expression and its function of SET7/9, a histone methyltransferase gene, in gastric cancer2016
Author(s)
Akiyama Y, Nishikawaji T, Shimada S, Sakamoto A, Deng D, Kim WH, Zhu WG, Yuasa Y, Tanaka S.
Organizer
The 35th Sapporo International Cancer Symposium
Place of Presentation
ロイトン札幌, 札幌
Year and Date
2016-06-24
Related Report
Int'l Joint Research
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