Functional analysis of a histone methyltransferase in colorectal cancer by comprehensive genome analysis

• Project/Area Number: 23310137
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical genome science
• Research Institution: The University of Tokyo
• Principal Investigator: FURUKAWA Yoichi 東京大学, 医科学研究所, 教授 (20272560)
• Co-Investigator(Kenkyū-buntansha): IKENOUE Tsuneo 東京大学, 医科学研究所, 准教授 (80396712) ; YAMAGUCHI Rui 東京大学, 東京大学, 講師 (90380675) ; YAMAGUCHI Kiyoshi 東京大学, 医科学研究所, 助教 (50466843)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥20,540,000 (Direct Cost: ¥15,800,000、Indirect Cost: ¥4,740,000); Fiscal Year 2013: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2012: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2011: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
• Keywords: 疾患関連遺伝子 / ゲノム / 大腸がん / ヒストン / メチル基転移酵素 / 大腸癌

Research Abstract

Expression profile analysis using colon cancer cells treated with SMYD3-specific siRNA identified a total of 1543 genes (entities) that were significantly upregulated by SMYD3. Subsequent in silico analysis using MetaGP revealed that these genes are potentially controlled by 126 transcription factors. Combined with the data of ChIP on chip analysis using anti-SMYD3 antibody, we identified 110 candidates of target genes of SMYD3. In addition, gene ontology and gene set enrichment analyses elucidated that elevated SMYD3 expression is associated with cell cycle control. These data suggest that SMYD3 plays a crucial role in proliferation of cancer cells and that inhibition of its function should be a rational strategy to treat human cancers.

Research Products

• [Journal Article] Identification of two Wnt-responsive elements in the intron of RING Finger Protein 43 (RNF43) gene (2014)
  • Author(s): Takahashi N, Yamaguchi K, Ikenoue T, Fujii T, Furukawa Y
  • Journal Title: PLoS ONE Volume: 9
• [Journal Article] Overexpression of cohesion establishment factor DSCC1 through E2F in colorectal cancer (2014)
  • Author(s): Yamaguchi K, Yamaguchi R, Takahashi N, Ikenoue T, Fujii T, Shinozaki M, Tsurita G, Hata K, Niida A, Imoto S, Miyano S, Nakamura Y, Furukawa Y
  • Journal Title: PLoS ONE Volume: 9
• [Journal Article] Identification of two Wnt-responsive elements in the intron of RING Finger Protein 43 (RNF43) gene. (2014)
  • Author(s): Takahashi N, Yamaguchi K, Ikenoue T, Fujii T, Furukawa Y.
  • Journal Title: PLoS ONE Volume: 9 Issue: 1 Pages: e86582-e86582
  • DOI: 10.1371/journal.pone.0086582
  • Peer Reviewed
• [Journal Article] Overexpression of cohesion establishment factor DSCC1 through E2F in colorectal cancer. (2014)
  • Author(s): Yamaguchi K, Rui Yamaguchi R, Takahashi N, Ikenoue T, Fujii T, Shinozaki M, Tsurita G, Hata K, Niida A, Imoto S, Miyano S, Nakamura Y, Furukawa Y
  • Journal Title: PLoS ONE Volume: 9 Issue: 1 Pages: e85750-e85750
  • DOI: 10.1371/journal.pone.0085750
  • Peer Reviewed
• [Journal Article] Early detection of metachronous bile duct cancer in Lynch syndrome : report of a case (2013)
  • Author(s): Shigeyasu K, Tanakaya K, Nagasaka T, Aoki H,Fujiwara T, Sugano K, Ishikawa H, Yoshida T, Moriya Y, Furukawa Y, Goel A, Takeuchi H.
  • Journal Title: Surg Today
• [Journal Article] Wnt3a stimulates maturation of impaired neutrophils developed from severe congenital neutropenia patient-derived pluripotent stem cells (2013)
  • Author(s): Hiramoto T, Ebihara Y, Mizoguchi Y, Nakamura K, Yamaguchi K, Ueno K, Michizuki S, Yamamoto S, Nagasaki M, Furukawa Y, Tani K, Nakauchi H, Kobayashi M, Tsuji K
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 110(8) Pages: 3023-3028
• [Journal Article] Quantitative PCR detection of CEP110-FGFR1 fusion gene in a patient with 8p11 syndrome (2013)
  • Author(s): Yamamoto S, Ebihara Y, Mochizuki S, Kawakita T,Kato S, Ooi J, Tojo A, Yusa N, Furukawa Y, Oyaizu N, Watanabe J, Sato K, Kimura F, and Tsuji K
  • Journal Title: Leukemia & Lymphoma Volume: 54(9) Pages: 2068-9
• [Journal Article] Wnt3a stimulates maturation of impaired neutrophils developed from severe congenital neutropenia-derived pluipotent stem cells with heterozygous ELANE mutation. (2013)
  • Author(s): Hiramoto T
  • Journal Title: Proc Natl Acad Sci USA Volume: 110 Issue: 8 Pages: 3023-3028
  • DOI: 10.1073/pnas.1217039110
  • Peer Reviewed
• [Journal Article] Quantitative PCR detection of CEP110-FGFR1 fusion gene in a patient with 8p11 syndrome. (2013)
  • Author(s): Yamamoto S, Ebihara Y, Mochizuki S, Kawakita T, Kato S, Ooi J, Takahashi S, Tojo A, Yusa N, Furukawa Y, Oyaizu N, Watanabe J, Sato K, Kimura F, Tsuji K.
  • Journal Title: Leukemia and Lymphoma Volume: 54 Issue: 9 Pages: 2068-2069
  • DOI: 10.3109/10428194.2013.767455
  • Peer Reviewed
• [Journal Article] Aberrant splicing caused by a MLH1 splice donor site mutation found in a young Japanese patient with Lynch syndrome (2012)
  • Author(s): Takahashi M, Furukawa Y, Shimodaira H, Sakayori M, Moriya T, Moriya Y, Nakamura Y, Ishioka C
  • Journal Title: Fam Cancer Volume: 11(4) Pages: 559-64
• [Journal Article] CLCA2 as a p53-inducible senescence mediator (2012)
  • Author(s): Tanikawa C, Nakagawa H, Furukawa Y, Nakamura Y, Matsuda K
  • Journal Title: Neoplasia Volume: 14(2) Pages: 141-9
• [Journal Article] CLCA2 as a p53-inducible senescence mediator (2012)
  • Author(s): C.Tanikawa, H.Nakagawa, Y.Furukawa, Y.Nakamura, K.Matsuda
  • Journal Title: Neoplasia Volume: 14 Issue: 2 Pages: 141-149
  • DOI: 10.1593/neo.111700
  • Peer Reviewed
• [Journal Article] MRG-binding protein contributes to colorectal cancer development (2011)
  • Author(s): Yamaguchi K, Sakai M, Kim J, Tsunesumi S, Fujii T, Ikenoue T, Yamada Y, Akiyama Y, Muto Y, Yamaguchi R, Miyano S, Nakamura Y, Furukawa Y
  • Journal Title: Cancer Sci Volume: 102(8) Pages: 1486-92
  • NAID: 10030242078
• [Journal Article] Smyd3 is required for the development of cardiac and skeletal muscle in zebrafish (2011)
  • Author(s): Fujii T, Tsunesumi S, Yamaguchi K, Watanabe S, & Furukawa Y
  • Journal Title: PLoS One Volume: 6(8)
• [Journal Article] SMYD3 interacts with HTLV-1 Tax and regulates sub-cellular localization of Tax (2011)
  • Author(s): Yamamoto K, Ishida T, Nakano K, Yamagishi M, Yamochi T, Tanaka Y, Furukawa Y, Nakamura Y, Watanabe T
  • Journal Title: Cancer Science Volume: 102 Pages: 260-266
  • NAID: 10029289377
• [Journal Article] Smyd3 is required for the development of cardiac and skeletal muscle in zebrafish (2011)
  • Author(s): Fujii T, Tsunesumi S, Yamaguchi K, Watanabe S, Furukawa Y
  • Journal Title: PLoS One Volume: 6
  • Peer Reviewed
• [Journal Article] MRG-binding protein contributes to colorectal cancer development (2011)
  • Author(s): Yamaguchi K, Sakai M, Kim J, Tsunesumi S, Fujii T, Ikenoue T, Yamada Y, Akiyama Y, Muto Y, Yamaguchi R, Miyano S, Nakamura Y, Furukawa Y
  • Journal Title: Cancer Science Volume: 102 Pages: 1486-1492
  • NAID: 10030242078
  • Peer Reviewed
• [Journal Article] A case of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) with multiple polyps arising in the cecum and appendix (2011)
  • Author(s): Kaneko M, Nozawa H, Kitayama J, Sunami E, Akahane M, Yamauchi N, Furukawa Y, Nagawa H
  • Journal Title: Acta Gastroenterol Belg Volume: 74 Pages: 352-354
  • Peer Reviewed
• [Presentation] 家族性腫瘍基礎と臨床 (2013)
  • Organizer: 第22回日本癌学会市民公開講座
  • Place of Presentation: 横浜
  • Year and Date: 2013-10-05
• [Presentation] 患者さんひとりひとりの治療のために (2013)
  • Organizer: 第22回日本癌学会市民公開講座
  • Place of Presentation: 横浜
  • Year and Date: 2013-10-05
• [Presentation] Identification of a single nucleotide polymorphism associated with SIAJ2 expression (2013)
  • Organizer: 第22回日本癌学会市民公開講座
  • Place of Presentation: 横浜
  • Year and Date: 2013-10-04
• [Presentation] リングフィンガープロテイン43 の転写調節機構 (2013)
  • Organizer: 第22回日本癌学会市民公開講座
  • Place of Presentation: 横浜
  • Year and Date: 2013-10-03
• [Presentation] 次世代シークエンサーがもたらす近未来の医療 (2013)
  • Organizer: 第19回日本家族性腫瘍学会学術集会
  • Place of Presentation: 大分
  • Year and Date: 2013-07-27
• [Presentation] DSCC1 is a novel biomarker for chemo-resistant colorectal cancer (2013)
  • Organizer: The 9th AACR-JCA- Joint Conference
  • Place of Presentation: Hawaii USA
  • Year and Date: 2013-02-23
• [Presentation] 家族性腫瘍 基礎と臨床 (2013)
  • Author(s): 古川洋一
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] リングフィンガープロテイン43の転写調節機構および下流遺伝子解析 (2013)
  • Author(s): 髙橋則彦 山口貴世志 池上恒雄 古川洋一
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Idenntification of a single nucleotide polymorphism associated with SIAH2 expression (2013)
  • Author(s): Seham Elgazzar 髙橋則彦 山口貴世志 前仏均 片桐豊雅 池上恒雄 中村祐輔 古川洋一
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] DSCC1 is a novel biomarker for chemo-resistant colorectal cancer. (2013)
  • Author(s): Kiyoshi Yamaguchi, Rui Yamaguchi, Masaru Shinozaki, GIichiro Tsurita, Keisuke Hata, Seiya Imoto, Satoru Miyano, Yusuke Nakamura, Yoichi Furukawa
  • Organizer: The 9th AACR-JCA Joint Conference
  • Place of Presentation: Maui HI, USA
• [Presentation] DSCC1 promotes survival of colorectal cancer cells through the inhibition of BCL2 expression (2012)
  • Organizer: The 8th Symposium on Cancer Research and Therapy
  • Place of Presentation: 東京
  • Year and Date: 2012-11-10
• [Presentation] Identifying the target of histone methyltransferase SMYD3 in colorectal cancer cells (2012)
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-21
• [Presentation] Smyd3 is required for the development of heart and skeletal muscle in zebrafish (2012)
  • Organizer: KEYSTONE SYMPOSIA Epigenomics
  • Place of Presentation: Keystone, Colorado, USA
  • Year and Date: 2012-01-18
• [Presentation] Identifying the target of histone methyltransferase SMYD3 in colorectal cancer cells (2012)
  • Author(s): 山口貴世志、池上恒雄、宮野悟、中村祐輔、古川洋一
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌（札幌）
• [Presentation] DSCC1 promotes survival of colorectal cancer cells through the inhibition of BCL2 expression (2012)
  • Author(s): Kiyoshi Yamaguchi, Rui Yamaguchi, Masaru Shinozaki, GIichiro Tsurita, Keisuke Hata, Seiya Imoto, Satoru Miyano, Yusuke Nakamura, Yoichi Furukawa
  • Organizer: The 8th, International Symposium on Cancer Research and Therapy
  • Place of Presentation: 東京会館（東京）
• [Presentation] Defective in sister chromatoid cohesion 1 homolog (DSCC1), a novel target of E2F1 is overexpressed in colorectal cancer (2011)
  • Organizer: 第70回日本癌学会学術総
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-04
• [Presentation] Defective in sister chromatoid cohesion 1 homolog (DSCC1), a novel target of E2F1 is overexpressed in colorectal cancer (2011)
  • Author(s): 山口貴世志、藤井智明、池上恒雄、中村祐輔、古川洋一
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-04
• [Presentation] MRGBP (C20orf20) contributes to development of colorectal cancer (2011)
  • Author(s): Kiyoshi Yamaguchi, Michihiro Sakai, Joohun Kim, Yoshinao Yamada, Yoshiyuki Akiyama, Yusuke Nakamura, Yoichi Furukawa
  • Organizer: The 102th. Annual meeting of American Association for Cancer Research
  • Place of Presentation: Orlando FL, USA
  • Year and Date: 2011-04-04
• [Remarks]
  • URL: http://www.ims.u-tokyo.ac.jp/furukawa/index.html
• [Remarks] 東京大学医科学研究所
  • URL: http://www.ims.u-tokyo.ac.jp/imsut/jp/