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Aberrant hydroxymethylation in human liver cancer

Research Project

Project/Area Number 25860521
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Gastroenterology
Research InstitutionThe University of Tokyo

Principal Investigator

NAGAE Genta  東京大学, 先端科学技術研究センター, 特任講師 (10587348)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords肝臓病学 / エピジェネティクス / 肝臓学
Outline of Final Research Achievements

Methylation profiles of hepatocellular carcinoma (HCC) have revealed aberrant hypermethylation and hypomethylation, which form four subgroups. However, molecular significance of aberrant hypomethylation in HCC remains poorly understood. Here, we performed comprehensive profiling of cytosine methylation and hydroxymethylation (5-hmC) for the TET1-upregulated HCCs and clarified the aberrant deposition of 5-hmC in a genome-wide manner. Knockdown of endogenous TET1 in hepatoma cell lines decreased hmC deposition with cell growth suppression. Collectively, these results indicate the novel function of methylcytosine dioxygenase TET1 that promotes cell proliferation though epigenetic dysregulation of the oncogenic targets during hepatocarcinogenesis.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (28 results)

All 2016 2015 2014 2013 Other

All Journal Article (19 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 17 results,  Open Access: 8 results,  Acknowledgement Compliant: 3 results) Presentation (7 results) (of which Invited: 1 results) Remarks (2 results)

  • [Journal Article] Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution.2016

    • Author(s)
      R. Uchi (他40名, 山本36番目)
    • Journal Title

      PLoS Genetics

      Volume: 12 Issue: 2 Pages: 1-24

    • DOI

      10.1371/journal.pgen.1005778

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prognostic significance of CpG island methylator phenotype in surgically resected small cell lung carcinoma2016

    • Author(s)
      Saito Y, Nagae G, Motoi N, Miyauchi E, Ninomiya H, Uehara H, Mun M, Okumura S, Ohyanagi F, Nishio M, Satoh Y, Aburatani H, Ishikawa Y.
    • Journal Title

      Cancer Sci.

      Volume: 107 Issue: 3 Pages: 320

    • DOI

      10.1111/cas.12876

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Integrated molecular analysis of adult T cell leukemia/lymphoma.2015

    • Author(s)
      Kataoka K, Nagata Y, Kitanaka A, Shiraishi Y, Shimamura T, Yasunaga J, Totoki Y, Chiba K, Sato-Otsubo A, Nagae G, et al.
    • Journal Title

      Nat Genet.

      Volume: 47(11) Issue: 11 Pages: 1304-15

    • DOI

      10.1038/ng.3415

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Integrated genetic and epigenetic analysis defines novel molecular subgroups in rhabdomyosarcoma.2015

    • Author(s)
      Seki M, Nishimura R, Yoshida K, Shimamura T, Shiraishi Y, Sato Y, Kato M, Chiba K, Tanaka H, Hoshino N, Nagae G, Shiozawa Y, Okuno Y, Hosoi H, Tanaka Y, Okita H, Miyachi M, Souzaki R, Taguchi T, Koh K, Hanada R, Kato K, Nomura Y, Akiyama M, Oka A, Igarashi T, Miyano S, Aburatani H, Hayashi Y, Ogawa S, Takita J.
    • Journal Title

      Nat Commun.

      Volume: 6 Issue: 1 Pages: 7557-7557

    • DOI

      10.1038/ncomms8557

    • NAID

      120005623266

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Age-Dependent Decrease of DNA Hydroxymethylation in Human T Cells2015

    • Author(s)
      Truong TP, Sakata-Yanagimoto M, Yamada M, Nagae G, Enami T, Nakamoto-Matsubara R, Aburatani H, Chiba S.
    • Journal Title

      Journal of Clinical and Experimental Hematopathology

      Volume: 55 Issue: 1 Pages: 1-6

    • DOI

      10.3960/jslrt.55.1

    • NAID

      130005083797

    • ISSN
      1346-4280, 1880-9952
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] BRCC3 mutations in myeloid neoplasms.2015

    • Author(s)
      Huang D, Nagata Y, Grossmann V, Radivoyevitch T, Okuno Y, Nagae G, et al.
    • Journal Title

      Haematologica.

      Volume: 100(8) Pages: 1051-7

    • DOI

      10.3324/haematol.2014.111989

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] がん研究におけるシングルセル遺伝子解析2015

    • Author(s)
      永江玄太
    • Journal Title

      実験医学 2015年1月号 Vol.33 No.1 シングルセル生物学

      Volume: 33 Pages: 7-14

    • Related Report
      2014 Research-status Report
  • [Journal Article] Trans-ancestry mutational landscape of hepatocellular carcinoma genomes.2014

    • Author(s)
      Totoki Y, Tatsuno K, Covington KR, Ueda H, Creighton CJ, Kato M, Tsuji S, Donehower LA, Slagle BL, Nakamura H, Yamamoto S, Shinbrot E, Hama N, Lehmkuhl M, Hosoda F, Arai Y, Walker K, Dahdouli M, Gotoh K, Nagae G, Gingras MC, Muzny DM, …, Takayama T, Fukayama M, Gibbs RA, Wheeler DA, Aburatani H, Shibata T
    • Journal Title

      Nat Genet.

      Volume: 46 Issue: 12 Pages: 1267-73

    • DOI

      10.1038/ng.3126

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hes1 promotes blast crisis in chronic myelogenous leukemia through MMP-9 upregulation in leukemic cells.2014

    • Author(s)
      Nakahara F, Kitaura J, Uchida T, Nishida C, Togami K, Inoue D, Matsukawa T, Kagiyama Y, Enomoto Y, Kawabata KC, Chen-Yi L, Komeno Y, Izawa K, Oki T, Nagae G, Harada Y, Harada H, Otsu M, Aburatani H, Heissig B, Hattori K, Kitamura T.
    • Journal Title

      Blood

      Volume: 123(25) Issue: 25 Pages: 3932-42

    • DOI

      10.1182/blood-2013-01-476747

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Methionine metabolism regulates maintenance and differentiation of human pluripotent stem cells.2014

    • Author(s)
      Shiraki, N., Shiraki, Y., Tsuyama, T., Obata, F., Miura, M., Nagae, G., Aburatani, H., Kume, K., Endo, F., and Kume, S.
    • Journal Title

      Cell Metab.

      Volume: 19 Issue: 5 Pages: 780-794

    • DOI

      10.1016/j.cmet.2014.03.017

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 全ゲノムメチル化解析からみえてきたがん細胞のメチル化異常2014

    • Author(s)
      永江玄太
    • Journal Title

      実験医学増刊 Vol.32 No.12 個別化医療を拓くがんゲノム研究

      Volume: 32 Pages: 67-71

    • Related Report
      2014 Research-status Report
  • [Journal Article] Concurrent Activation of Acetylation and Tri-Methylation of H3K27 in a Subset of Hepatocellular Carcinoma with Aggressive Behavior2014

    • Author(s)
      Hayashi A, Yamauchi N, Shibahara J, Kimura H, Morikawa T, Ishikawa S, Nagae G, Nishi A, Sakamoto Y, Kokudo N, Aburatani H, Fukayama M.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 3 Pages: e91330-e91330

    • DOI

      10.1371/journal.pone.0091330

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] H3F3A K27M mutations in thalamic gliomas from young adult patients2014

    • Author(s)
      Aihara K, Mukasa A, Gotoh K, Saito K, Nagae G, Tsuji S, Tatsuno K, Yamamoto S, Takayanagi S, Narita Y, Shibui S, Aburatani H, Saito N
    • Journal Title

      Neuro Oncol

      Volume: 16 Issue: 1 Pages: 140-146

    • DOI

      10.1093/neuonc/not144

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Landscape of genetic lesions in 944 patients with myel odysplastic syndromes.2014

    • Author(s)
      Haferlach T, Nagata Y, Grossmann V, Okuno Y, Bacher U, Nagae G, Schnittger S, Sanada M, Kon A, Alpermann T, Yoshida K, Roller A, Nadarajah N, Shiraishi Y, Shiozawa Y, Chiba K, Tanaka H, Koeffler HP, Klein HU, Dugas M, Aburatani H, Kohlmann A, Miyano S, Haferlach C, Kern W, Ogawa S.
    • Journal Title

      Leukemia

      Volume: 28(2) Issue: 2 Pages: 241-7

    • DOI

      10.1038/leu.2013.336

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Concurrent loss of Ezh2 and Tet2 cooperates in the pathogenesis of myelodysplastic disorders.2013

    • Author(s)
      Muto T, Sashida G, Oshima M, Wendt GR, Mochizuki-Kashio M, Nagata Y, Sanada M, Miyagi S, Saraya A, Kamio A, Nagae G, Nakaseko C, Yokote K, Shimoda K, Koseki H, Suzuki Y, Sugano S, Aburatani H, Ogawa S, Iwama A.
    • Journal Title

      The Journal of Experimental Medicine

      Volume: 210(12) Issue: 12 Pages: 2627-39

    • DOI

      10.1084/jem.20131144

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms.2013

    • Author(s)
      Kon A, Yoshida K
    • Journal Title

      Nature Genet.

      Volume: 45 Issue: 10 Pages: 1232-1237

    • DOI

      10.1038/ng.2731

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Integrated molecular analysis of clear-cell renal cell carcinoma.2013

    • Author(s)
      Sato Y, Yoshida K
    • Journal Title

      Nature Genet.

      Volume: 45 Issue: 8 Pages: 860-867

    • DOI

      10.1038/ng.2699

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Histone demethylase KDM4C regulates sphere formation by mediating the cross talk between Wnt and Notch pathways in colonic cancer cells2013

    • Author(s)
      Yamamoto S, Tateishi K, Kudo Y, Yamamoto K, Isagawa T, Nagae G, Nakatsuka T, Asaoka Y, Ijichi H, Hirata Y, Otsuka M, Ikenoue T, Aburatani H, Omata M, Koike K.
    • Journal Title

      Carcinogenesis

      Volume: 34 Issue: 10 Pages: 2380

    • DOI

      10.1093/carcin/bgt174

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The role of NF-κB signaling in the maintenance of pluripotency of human induced pluripotent stem cells2013

    • Author(s)
      Takase O, Yoshikawa M, Idei M, Hirahashi J, Fujita T, Takato T, Isagawa T, Nagae G, Suemori H, Aburatani H, Hishikawa K
    • Journal Title

      PLoS One

      Volume: 8(2) Issue: 2 Pages: e56399-e56399

    • DOI

      10.1371/journal.pone.0056399

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 肝がんにおけるエンハンサー領域のエピゲノム異常2015

    • Author(s)
      永江玄太、Renard-Guillet Claire、辰野健二、山本尚吾、上田宏生、林玲匡、緑川泰、中川英刀、柴田龍弘、油谷浩幸
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2015-10-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] TET1の発現上昇はエンハンサー領域の異常ヒドロキシメチル化を介して肝細胞癌の悪性形質を促進する2015

    • Author(s)
      永江玄太、白井聖一、関元昭、工藤洋太郎、神尾明日香、緑川泰、立石敬介、一瀬雅夫、油谷浩幸
    • Organizer
      第9回エピジェネティクス研究会
    • Place of Presentation
      学術総合センター(東京都)
    • Year and Date
      2015-05-25
    • Related Report
      2015 Annual Research Report
  • [Presentation] TET1 promotes malignant characteristics by aberrant enhancer hydroxymethylation in hepatocellular carcinoma.2015

    • Author(s)
      Nagae G, Shirai K, Seki M, Kamio A, Midorikawa Y, Tateishi K, Ichinose M, Aburatani H.
    • Organizer
      Keystone Symposia, DNA methylation
    • Place of Presentation
      Keystone、USA
    • Year and Date
      2015-04-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] TET1 promotes malignant characteristics by aberrant enhancer hydroxymethylation in hepatocellular carcinoma2014

    • Author(s)
      Genta Nagae, Hiroyuki Aburatani
    • Organizer
      The 73th Japan Cancer Association Annual Meeting
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Single cell transcriptome analysis of liver cancer stem cells2014

    • Author(s)
      Genta Nagae, Hiromitsu Ito, Shinji Tanaka, Hiroyuki Aburatani
    • Organizer
      Keystone symposia
    • Place of Presentation
      Banff, Canada
    • Related Report
      2013 Research-status Report
  • [Presentation] Cytosine methylation dynamics during hepatic differentiation2013

    • Author(s)
      永江玄太 ・ 白木伸明 ・神尾明日香 ・藤田隆教 ・粂昭苑・ 油谷浩幸
    • Organizer
      第7回エピジェネティクス研究会
    • Place of Presentation
      奈良
    • Related Report
      2013 Research-status Report
  • [Presentation] Variable patterns of aberrant promoter methylation in clinical cancer tissues2013

    • Author(s)
      Genta Nagae, Shingo Tsuji, Hiroyuki Aburatani
    • Organizer
      第72回日本癌学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Remarks] 東京大学先端科学技術研究センター ゲノムサイエンス分野

    • URL

      http://www.genome.rcast.u-tokyo.ac.jp/

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
  • [Remarks] 東京大学先端科学技術研究センター

    • URL

      http://www.rcast.u-tokyo.ac.jp/research/people/staff-nagae_genta_ja.html

    • Related Report
      2015 Annual Research Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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