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Systems analysis of roles of non-coding RNAs in lung cancer development

Planned Research

Project AreaConquering cancer through neo-dimensional systems understanding
Project/Area Number 15H05910
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Complex systems
Research InstitutionAichi Cancer Center Research Institute (2018-2019)
Nagoya University (2015-2017)

Principal Investigator

Takahashi Takashi  愛知県がんセンター(研究所), 総長, 総長 (50231395)

Co-Investigator(Kenkyū-buntansha) 梶野 泰祐  愛知県がんセンター(研究所), 分子診断TR分野, 主任研究員 (50723673)
細野 祥之  愛知県がんセンター(研究所), がん標的治療TR分野, ユニット長 (60820363)
中杤 昌弘  名古屋大学, 医学部附属病院, 病院講師 (10559983)
柳澤 聖  名古屋大学, 医学系研究科, 講師 (20372112)
長田 啓隆  愛知県がんセンター(研究所), 分子腫瘍, 室長 (30204176)
Project Period (FY) 2015-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥238,810,000 (Direct Cost: ¥183,700,000、Indirect Cost: ¥55,110,000)
Fiscal Year 2019: ¥42,250,000 (Direct Cost: ¥32,500,000、Indirect Cost: ¥9,750,000)
Fiscal Year 2018: ¥42,380,000 (Direct Cost: ¥32,600,000、Indirect Cost: ¥9,780,000)
Fiscal Year 2017: ¥42,380,000 (Direct Cost: ¥32,600,000、Indirect Cost: ¥9,780,000)
Fiscal Year 2016: ¥42,250,000 (Direct Cost: ¥32,500,000、Indirect Cost: ¥9,750,000)
Fiscal Year 2015: ¥69,550,000 (Direct Cost: ¥53,500,000、Indirect Cost: ¥16,050,000)
Keywords癌 / システム生物学 / ノンコーディングRNA / 肺がん
Outline of Final Research Achievements

The involvement of long non-coding RNAs (lncRNAs) in the pathogenesis of lung cancers has not been well elucidated, in contrast to great advance in studies on miRNA alterations. In this study, we utilized an integrative approach employing systems biology and detailed molecular biological analyses, which consequently allowed us to identify novel lncRNAs, which forms regulatory network with crucial cancer-related transcription factors including MYC, p53 and TTF-1.

Academic Significance and Societal Importance of the Research Achievements

蛋白質に関する情報はヒトゲノムの2%以下に過ぎない一方で、70%を超える領域はRNAに転写されている。ノンコーティングRNA(ncRNA)の一種であるマイクロRNAに比して、長鎖ncRNA(lncRNA)のがんにおける役割解明は大きく遅れている。本研究課題の成果は、肺がんの発生・進展に重要な転写因子のMYC, p53, TTF-1の制御に関わる、新規lncRNAの同定とその分子機能の解明に初めて成功したものであり学術的意義は高い。また、システム生物学とがん研究を高度に融合した研究アプローチの有用性を端的に示した点でも意義が高い。今後の創薬開発などへの発展も期待されるなど社会的な意義も高い。

Report

(6 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (28 results)

All 2020 2019 2018 2017 2016 2015 Other

All Journal Article (13 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 13 results,  Open Access: 12 results,  Acknowledgement Compliant: 1 results) Presentation (14 results) (of which Int'l Joint Research: 5 results,  Invited: 6 results) Remarks (1 results)

  • [Journal Article] ROR1-CAVIN3 interaction required for caveolae-dependent endocytosis and pro-survival signaling in lung adenocarcinoma2019

    • Author(s)
      Yamaguchi T, Hayashi M, Ida L, Yamamoto M, Lu C, Kajino T, Cheng J, Nakatochi M, Isomura H, Yamazaki M, Suzuki M, Fujimoto T, Takahashi T.
    • Journal Title

      Oncogene

      Volume: - Issue: 26 Pages: 5142-5157

    • DOI

      10.1038/s41388-019-0785-7

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction2019

    • Author(s)
      Kajino T, Shimamura T, Gong S, Yanagisawa K, Ida L, Nakatochi M, Griesing S, Shimada Y, Kano K, Suzuki M, Miyano S
    • Journal Title

      EMBO J

      Volume: 38 Issue: 17 Pages: 1-13

    • DOI

      10.15252/embj.201798441

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Translating gene signatures into a pathological feature: Tumor necrosis predicts disease relapse in operable and stage I lung adenocarcinoma.2018

    • Author(s)
      Lin EP, Hsiao TH, Lu JY, Wong SH, Lu TP, Peck K, Takahashi T, Yang, PC.
    • Journal Title

      JCO Precision Oncology

      Volume: 2 Issue: 2 Pages: 1-13

    • DOI

      10.1200/po.18.00043

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Expression of P-REX2a is associated with poor prognosis in endometrial malignancies2018

    • Author(s)
      Takeshita Sho、Yamashita Yoriko、Shiomi Kosuke、Suzuki Nako、Yoshida Jun、Naiki-Ito Aya、Suzuki Shugo、Akatsuka Shinya、Toyokuni Shinya、Takahashi Takashi、Mase Shoko、Arakawa Atsushi、Sugiura-Ogasawara Mayumi、Takahashi Satoru
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 37 Pages: 5489-5495

    • DOI

      10.18632/oncotarget.25349

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Helicobacter pylori infection is associated with favorable outcome in advanced gastric cancer patients treated with S-1 adjuvant chemotherapy.2018

    • Author(s)
      Nishizuka SS, Tamura G, Nakatochi M, Fukushima N, Ohmori Y, Sumida C, Iwaya T, Takahashi T, Koeda K; Northern Japan Gastric Cancer Study Consortium.
    • Journal Title

      J Surg Oncol

      Volume: - Issue: 5 Pages: 947-956

    • DOI

      10.1002/jso.24977

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Thyroid transcription factor-1-regulated miR-532-5p targets KRAS and MKL2 oncogenes and induces apoptosis in lung adenocarcinoma cells2017

    • Author(s)
      Griesing, S, Kajino T, Tai MC, Liu Z, Nakatochi M, Shimada Y, Suzuki M, Takahashi T
    • Journal Title

      Cancer Sci

      Volume: 108 Issue: 7 Pages: 1394-1404

    • DOI

      10.1111/cas.13271

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inactivating mutations and hypermethylation of the NKX2-1/TTF-1 gene in non-terminal respiratory unit-type lung adenocarcinomas.2017

    • Author(s)
      Matsubara D, Soda M, Yoshimoto T, Amano Y, Sakuma Y, Yamato A, Ueno T, Kojima S, Shibano T, Hosono Y, Kawazu M, Yamashita Y, Endo S, Hagiwara K, Fukayama M,Takahashi T, Mano H, Niki T.
    • Journal Title

      Cancer Sci

      Volume: 108 Issue: 9 Pages: 1888-1896

    • DOI

      10.1111/cas.13313

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fenton reaction-induced renal carcinogenesis in Mutyh-deficient mice exhibits less chromosomal aberrations than the rat model.2017

    • Author(s)
      Li GH, Akatsuka S, Chew SH, Jiang L, Nishiyama T, Sakamoto A, Takahashi T, Futakuchi M, Suzuki H, Sakumi K, Nakabeppu Y, Toyokuni S.
    • Journal Title

      Pathol Int.

      Volume: 67 Issue: 11 Pages: 564-574

    • DOI

      10.1111/pin.12598

    • NAID

      120006382249

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TTF-1/NKX2-1 binds to DDB1 and confers replication stress resistance to lung adenocarcinomas.2016

    • Author(s)
      Liu Z, Yanagisawa K, Griesing S, Iwai M, Kano K, Hotta N, Kajino T, Suzuki M, and Takahashi T.
    • Journal Title

      Oncogene

      Volume: 524 Issue: 26 Pages: 1-9

    • DOI

      10.1038/onc.2016.524

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ROR1 sustains caveolae and survival signaling as a scaffold of cavin-1 and caveolin-12016

    • Author(s)
      Yamaguchi T, Lu C, Yanagisawa K, Can Lu, Usukura J, Cheng J, Hotta N, Shimada Y, Ida R, Isomura H, Suzuki M, Fujimoto T, Takahashi T
    • Journal Title

      Nat Commun

      Volume: 7 Issue: 1 Pages: 10060-10060

    • DOI

      10.1038/ncomms10060

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Targeting ceramide synthase 6-dependent metastasis-prone phenotype in lung cancer cells.2016

    • Author(s)
      Suzuki M, et al.
    • Journal Title

      J. Clin. Invest.

      Volume: 126 Issue: 1 Pages: 254-265

    • DOI

      10.1172/jci79775

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Receptor tyrosine kinase-like orphan receptor 1, a target of NKX2-1/TTF-1 lineage-survival oncogene, inhibits apoptosis signal-regulating kinase 1-mediated pro-apoptotic signaling in lung adenocarcinoma2016

    • Author(s)
      Ida L, Yamaguchi T, Yanagisawa K, Kajino T, Shimada Y, Suzuki M, Takahashi T
    • Journal Title

      Cancer Sci

      Volume: 107 Issue: 2 Pages: 155-161

    • DOI

      10.1111/cas.12858

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] miR-342-3p regulates MYC transcriptional activity via direct repression of E2F1 in human lung cancer.2015

    • Author(s)
      Tai MC, Kajino T, Nakatochi M, Arima C, Shimada Y, Suzuki M, Miyoshi H, Yatabe Y, Yanagisawa K, Takahashi T.
    • Journal Title

      Carcinogenesis

      Volume: 36 Pages: 1464-1473

    • DOI

      10.1093/carcin/bgv152

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Presentation] Divergent lncRNA MYMLR regulated MYC by eliciting DNA looping and promotoer-enhancer interaction.2020

    • Author(s)
      Takahashi T
    • Organizer
      International Conference on Cancer Systems Biology Beyond
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] システム生物学的な探索によるMYC制御lncRNA、MYMLRの同定と機能解明2019

    • Author(s)
      Kajino T, Shimamura T, Gong S, Yanagisawa K, Ida L, Nakatochi M, Griesing S, Shimada Y, Kano K, Suzuki M, Miyano S, Takahashi T
    • Organizer
      第42回日本分子生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction.2018

    • Author(s)
      Kajino T, Shimamura T, Gong S, Yanagisawa K, Nakatochi M, Griesing S, Shimada Y, Kano K, Suzuki M, Miyano S, Takahashi T
    • Organizer
      AACR Annual Meeting 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ROR1-CAVIN3 interaction required for caveolae-dependent endocytosis and pro-survival signaling in lung adenocarcinoma.2018

    • Author(s)
      Tomoya Yamaguchi, Miyu Hayashi, Lisa Ida, Can Lu, Taisuke Kajino, Jinglei Cheng, Hisanori Isomura, Motoshi Suzuki, Toyoshi Fujimoto, Takashi Takahashi.
    • Organizer
      第77回日本癌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] SRC is involved in the ROR1-sustained ASK1 inhibition.2018

    • Author(s)
      Lisa Ida, Tomoya Yamaguchi, Taisuke Kajino, Xiaoyi Shi, Miyuu Hanashi, Kiyoshi Yanagisawa, Yukako Shimada, Motoshi Suzuki, Takashi Takahashi
    • Organizer
      第77回日本癌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction2018

    • Author(s)
      Taisuke Kajino, Teppei Shimamura, Shuyi Gong, Kiyoshi Yanagisawa, Masahiro Nakatochi, Sebastian Griesing, Yukako Shimada, Keiko Kano, Motoshi Suzuki, Satoru Miyano, Takashi Takahashi
    • Organizer
      Keystone Symposia "DNA and RNA methylation"
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ROR1によるカベオラ形成と生存シグナルの維持機構2017

    • Author(s)
      山口知也、林美優、井田梨沙、Can Lu、梶野泰祐、Jinglei Cheng、磯村久徳、鈴木元、藤本豊士、高橋隆
    • Organizer
      第69回 日本細胞生物学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Systems biology-based identification of MYMLR lncRNA modulating MYC oncogene2017

    • Author(s)
      Taisuke Kajino, Teppei Shimamura, Gong Shuyi, Kiyoshi Yanagisawa, Masahiro Nakatochi, Sebastian Griesing , Yukako Shimada, Keiko Kano, Satoru Miyano, Takashi Takahashi
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ROR1 inhibits ASK1-mediated pro-apoptotic signaling in lung adenocarcinoma2017

    • Author(s)
      Lisa Ida, Tomoya Yamaguchi, Taisuke Kajino, Kiyoshi Yanagisawa, Yukako Shimada, Motoshi Suzuki, and Takashi Takahashi
    • Organizer
      AACR Annual Meeting 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ROR1: An Achilles Heel of Lung Cancer.2017

    • Author(s)
      Takahashi T
    • Organizer
      24th Asia Pacific Cancer Conference
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 受容体型チロシンキナーゼROR1による生存シグナル維持の分子基盤2017

    • Author(s)
      高橋隆
    • Organizer
      第21回日本がん分子標的治療学会学術集会
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 肺癌の発生と進展の分子機構の解明:基礎研究のこれまでとこれから2015

    • Author(s)
      高橋隆
    • Organizer
      第56回日本肺がん学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2015-11-26
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Identification of non-coding RNAs modulating MYC activity in human lung cancers2015

    • Author(s)
      Takahashi T
    • Organizer
      The 74th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] ROR1 functions as a scaffold of cavin-1 and CAV1, sustaining caveolae and RTK-mediated survival signaling in lung cancer2015

    • Author(s)
      Yamaguchi T, Yanagisawa K, Lu C, Isomura H, Suzuki M, Fujimoto T, Takahashi T
    • Organizer
      The 74th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Remarks] 名古屋大学大学院医学系研究科分子腫瘍学分野

    • URL

      https://www.med.nagoya-u.ac.jp/molcar/jp/research2.html

    • Related Report
      2015 Annual Research Report

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Published: 2015-07-02   Modified: 2022-11-04  

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