Development of a novel bioinformatics method to identify novel functional peptides in a genome and experimental verification of their anticancer effects

• Project/Area Number: 24710222
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical genome science
• Research Institution: Chiba University
• Principal Investigator: TAKAHASHI HIRO 千葉大学, 園芸学研究科, 准教授 (30454367)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: バイオインフォマティクス / 翻訳抑制 / がん / 情報工学 / 癌 / 医療・福祉 / 薬学 / 医療･福祉

Outline of Final Research Achievements

The objectives are outlined in the title. Accordingly, we developed a novel bioinformatics method. This method was applicable to various genomes, and the function of the identified peptides was confirmed empirically by a transient in vitro assay. Moreover, we observed in vitro inhibition of growth of a sarcoma, murine sarcoma Sendai (MUSS) by 4E-BP peptides that inhibited the growth of various carcinomas in vitro.

Research Products

• [Journal Article] Identification of novel Arabidopsis thaliana upstream open reading frames that control expression of the main coding sequences in a peptide sequence-dependent manner. (2015)
  • Author(s): Ebina I, Takemoto-Tsutsumi M, Watanabe S, Koyama H, Endo Y, Kimata K, Igarashi T, Murakami K, Kudo R, Ohsumi A, Noh AL, Takahashi H, Naito S, Onouchi H
  • Journal Title: Nucleic Acids Research Volume: 43 Issue: 3 Pages: 1562-1576
  • DOI: 10.1093/nar/gkv018
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Application of a combination of a knowledge-based algorithm and 2-stage screening to hypothesis-free genomic data on irinotecan-treated patients for identification of a candidate single nucleotide polymorphism related to an adverse effect (2014)
  • Author(s): Takahashi H., Sai K., Saito Y., Kaniwa N., Matsumura Y., Hamaguchi T., Shimada Y., Ohtsu A., Yoshino T., Doi T., Okuda H., Ichinohe R., Takahashi A., Doi A., Odaka Y., Okuyama M., Saijo N., Sawada J., Sakamoto H., and Yoshida T.
  • Journal Title: PLoS ONE Volume: 9 Issue: 8 Pages: e105160-e105160
  • DOI: 10.1371/journal.pone.0105160
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Analysis of gene expression profiles of soft tissue sarcoma using a combination of knowledge-based filtering with integration of multiple statistics (2014)
  • Author(s): Takahashi A., Nakayama R., Ishibashi N., Doi A., Ichinohe R., Ikuyo Y., Takahashi T., Marui S., Yasuhara K., Nakamura T., Sugita S., Sakamoto H., Yoshida T., Hasegawa T., and Takahashi H.
  • Journal Title: PLoS ONE Volume: 9 Issue: 9 Pages: e106801-e106801
  • DOI: 10.1371/journal.pone.0106801
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Changes in mRNA stability associated with cold stress in Arabidopsis cells (2013)
  • Author(s): Chiba Y, Mineta K, Hirai MY, Suzuki S, Kanaya S, Takahashi H, Onouchi H, Yamaguchi J, Naito S
  • Journal Title: Plant Cell Physiol Volume: 54 Issue: 2 Pages: 180-194
  • DOI: 10.1093/pcp/pcs164
  • NAID: 10031145661
  • Peer Reviewed / Open Access
• [Journal Article] Meta-analyses of microarays of Arabidopsis asymmetric leaves1 (as1), as2 and their modifying mutants reveal a critical role of the ETT pathway in stabilization of adaxial-abaxial patterning and cell division during leaf develonment. (2013)
  • Author(s): Takahashi, H., et al.
  • Journal Title: Plant Cell Physiol. Volume: 54(3) Issue: 3 Pages: 418-431
  • DOI: 10.1093/pcp/pct027
  • Peer Reviewed
• [Journal Article] Dual regulation of AUXIN-RESPONSE-FACTOR3 gene expression by AS1-AS2, which maintains the status of DNA methylation, is involved in stabilization of leaf adaxial-abaxial partitioning in Arabidopsis. (2013)
  • Author(s): Iwasaki, M., et al.
  • Journal Title: Development Volume: 140 Issue: 9 Pages: 1958-1969
  • DOI: 10.1242/dev.085365
  • Peer Reviewed
• [Journal Article] Predictive value of high-molecular weight adiponectin in subjects with a higher risk of the development of metabolic syndrome: From a population based 5-year follow-up data. (2013)
  • Author(s): Kotooka N, Komatsu A, Takahashi H, Nonaka M, Kawaguchi C, Komoda H, Asaka M, Abe S, Taguchi I, Toyoda S, Nishiyama M, Inoue T, Node K.
  • Journal Title: Int J Cardiol. Volume: 167(3) Issue: 3 Pages: 1068-70
  • DOI: 10.1016/j.ijcard.2012.10.066
  • Peer Reviewed
• [Journal Article] Macrophage migration inhibitory factor and stearoyl-CoA desaturase 1: Potential prognostic markers for soft tissue sarcomas based on bioinformatics analyses (2013)
  • Author(s): Takahashi H., Nakayama R., Hayashi S., Nemoto T., Murase Y., Nomura K., Takahashi T., Kubo K., Marui S., Yasuhara K., Nakamura T., Sueo T., Takahashi A., Tsutsumiuchi K., Ohta T., Kawai A., Sugita S., Yamamoto S., Kobayashi T., Honda H., Yoshida T., Hasegawa T.
  • Journal Title: PLoS ONE Volume: 8 Issue: 10 Pages: e78250-e78250
  • DOI: 10.1371/journal.pone.0078250
  • Peer Reviewed
• [Journal Article] Identification of a candidate single-nucleotide polymorphism related to chemotherapeutic response through a combination of knowledge-based algorithm and hypothesis-free genomic data (2013)
  • Author(s): Takahashi H., Kaniwa N., Saito Y., Sai K., Hamaguchi T., Shirao K., Shimada Y., Matsumura Y., Ohtsu A., Yoshino T., Takahashi A., Odaka Y., Okuyama M., Sawada J., Sakamoto H. and Yoshida T.
  • Journal Title: J. Biosci. Bioeng. Volume: 116 Issue: 6 Pages: 768-773
  • DOI: 10.1016/j.jbiosc.2013.05.021
  • NAID: 110009687843
  • Peer Reviewed
• [Journal Article] Reduced GNG2 expression levels in mouse malignant melanomas and human melanoma cell lines (2012)
  • Author(s): I. Yajima
  • Journal Title: Am. J. Cancer Res. Volume: 2 Pages: 322-329
  • Peer Reviewed
• [Journal Article] Berberine enhances defects in the establishment of leaf polarity in asymmetric leaves2 and asymmetric leaves1 of Arabidopsis thaliana (2012)
  • Author(s): Nakagawa A, Takahashi H, Kojima S, Sato N, Ohga K, Cha BY, Woo J-T, Nagai K, Horiguchi G, Tsukaya H, Machida Y and Machida C
  • Journal Title: Plant Mol Biol Volume: 79 Issue: 6 Pages: 569-581
  • DOI: 10.1007/s11103-012-9929-7
  • Peer Reviewed
• [Journal Article] BAIUCAS: a novel BLAST-based algorithm for the identification of upstream open reading frames with conserved amino acid sequences, and its application to the Arabidopsis thaliana genome (2012)
  • Author(s): H. Takahashi
  • Journal Title: Bioinformatics Volume: 28 Issue: 17 Pages: 2231-2241
  • DOI: 10.1093/bioinformatics/bts303
  • Peer Reviewed
• [Journal Article] Discovery of novel rules for G-quadruplex-forming sequences in plants by using bioinformatics methods. (2012)
  • Author(s): Takahashi H, et al.
  • Journal Title: J Biosci Bioeng Volume: 114(5) Issue: 5 Pages: 570-575
  • DOI: 10.1016/j.jbiosc.2012.05.017
  • NAID: 110009553595
  • Peer Reviewed
• [Presentation] Bioinformatic identification method of evolutional ranges for potential functional molecules on genomes (2014)
  • Author(s): Takahashi H., Takahashi A., Takemoto M., Ebina I., Kimata K., Igarashi T., Kudo R., Osumi A., Naito S., and Onouchi H.
  • Organizer: The Problem of the Origin of Life
  • Place of Presentation: Moscow, Russia
  • Year and Date: 2014-09-22 – 2014-09-26
• [Presentation] Analysis of gene expression profiles of soft tissue sarcoma using a combined method of knowledge-based filtering and integration of multiple statistics (2014)
  • Author(s): Takahashi H., Takahashi A.
  • Organizer: Computational Models in Biology and Medicine 2014
  • Place of Presentation: Cologne, Germany
  • Year and Date: 2014-09-18 – 2014-09-19
• [Presentation] Knowledge-based bioinformatic analyses of microarrays predict that epigenetic regulator AS1-AS2 controls cell division through ETTIN in leaf adaxial-abaxial patterning (2014)
  • Author(s): Takahashi H., Nakagawa A., Ishibashi N., Kojima S., Machida Y., and Machida C.
  • Organizer: 25th International Conference on Arabidopsis Research - ICAR2014
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2014-07-28 – 2014-08-01
• [Presentation] Chemical genetic analyses infer that AS1-AS2 controls cell division through ETTIN in leaf adaxial-abaxial and medio-lateral patterning (2014)
  • Author(s): Nakagawa A., Takahashi H., Ito T., Kojima S., Machida Y., and Machida C.
  • Organizer: 25th International Conference on Arabidopsis Research - ICAR2014
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2014-07-28 – 2014-08-01
• [Presentation] ASYMMETRIC LEAVES1 (AS1) and AS2 regulate the expression of AtIPT3 through AUXIN RESPONSE FACTOR3 / ETTIN function during leaf development in Arabidopsis thaliana (2014)
  • Author(s): Kojima S., Takahashi H., Ishibashi N., Handayani A., Matsumura Y., Machida Y., and Machida C.
  • Organizer: Auxins and Cytokinins in Plant Development-ACPD2014
  • Place of Presentation: Prague, Czech Republic
  • Year and Date: 2014-06-29 – 2014-07-04
• [Presentation] AS2 and BOB1 synergistically regulate cytokinin levels and the establishment of leaf adaxial-abaxial polarity through the ETT/ARF3-IPT3 pathway in Arabidopsis thaliana (2014)
  • Author(s): Ishibashi N., Kojima S., Kojima M., Sakakibara H., Takahashi H., Machida C., and Machida Y.
  • Organizer: International Symposium on Auxins and Cytokinins in Plant Development - ACPD2014
  • Place of Presentation: Prague, Czech Republic
  • Year and Date: 2014-06-29 – 2014-07-04
• [Presentation] 5'非翻訳領域にコードされた種間保存性ペプチドの網羅的探索・進化保存性評価手法の開発 (2013)
  • Author(s): 高橋広夫・高橋アンナ・竹本まり子・渡部峻・蝦名績・遠洞弥生・小山博彰・戸田智美・瀬戸隆太・内藤哲・尾之内均
  • Organizer: 第65回日本生物工学会大会
  • Place of Presentation: 広島国際会議場 (広島)
• [Presentation] 植物ゲノムの非コード領域からのバイオインフォマティクスによる有用情報抽出法 (2013)
  • Author(s): 高橋広夫
  • Organizer: 第3回植物RNA研究ネットワークシンポジウム
  • Place of Presentation: 北海道大学(札幌)
  • Invited
• [Presentation] Searching for the Leaf-shape-controlling Genes Downstream of AS1 & AS2 and its modifiers (2013)
  • Author(s): P. Prananingrum
  • Organizer: 第54回日本植物生理学会年会
  • Place of Presentation: 岡山大学(岡山)
• [Presentation] The ASYMMETRIC LEAVES1 (AS1)/AS2 Complex Is a Stabilizer for the Leaf Development in Arabidopsis (2013)
  • Author(s): Y. Machida
  • Organizer: 第54回日本植物生理学会年会
  • Place of Presentation: 岡山大学(岡山)
• [Presentation] シロイヌナズナの葉の形態形成に関わるASYMMETRIC LEAVES2下流因子のマイクロアレイ解析による探索 (2013)
  • Author(s): 小島晶子
  • Organizer: 第54回日本植物生理学会年会
  • Place of Presentation: 岡山大学(岡山)
• [Presentation] DNA損傷試薬は、シロイヌナズナの葉の向背軸分化を特異的に阻害する (2013)
  • Author(s): 中川彩美
  • Organizer: 第54回日本植物生理学会年会
  • Place of Presentation: 岡山大学(岡山)
• [Presentation] 5'非翻訳領域における種間保存性の高い上流ORFの網羅的探索法の開発 (2012)
  • Author(s): 高橋広夫
  • Organizer: 第44回化学工学会秋季大会
  • Place of Presentation: 東北大学(仙台)
• [Presentation] 5'非翻訳領域にコードされた種間保存性の高いペプチドの網羅的探索法の開発 (2012)
  • Author(s): 高橋広夫
  • Organizer: 第64回日本生物工学会大会
  • Place of Presentation: 神戸国際会議場(神戸)