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Identification of novel circular RNA in pancreatic cancer

Research Project

Project/Area Number 19H03430
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49010:Pathological biochemistry-related
Research InstitutionThe University of Tokyo

Principal Investigator

Otsuka Motoyuki  東京大学, 医学部附属病院, 講師 (90518945)

Co-Investigator(Kenkyū-buntansha) 丸山 玲緒  公益財団法人がん研究会, がん研究所 がんエピゲノムプロジェクト, プロジェクトリーダー (60607985)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords膵がん / 環状RNA / 膵癌 / 血清マーカー / マーカー
Outline of Research at the Start

本研究では、膵癌組織RNAを用いて、通常の解析では見落とされる可能性が高い環状RNA(Circular RNA)に特化したRNA sequencing を行い、in silico 解析も駆使して、これまで知られていなかった膵癌で高発現している新規のcircular RNAを取得し、その全貌解明と、バイオマーカーとしての有用性、および発癌過程における生物学的な機能を解析し、もって難治癌である膵癌の予後改善とともに、RNA研究分野の発展に学術的にも寄与することを目標とする。

Outline of Final Research Achievements

Circular RNAs (circRNAs) are single-stranded, covalently closed RNA molecules that are produced from pre-mRNAs. Although circRNAs are expressed under specific conditions, their comprehensive expression status is still unclear. Here, we performed a large-scale circRNA profiling analysis in human pancreatic ductal adenocarcinoma (PDAC) tissues. We identified more than 40,000 previously unknown circRNAs, some of which were upregulated in PDAC tissues, compared with normal pancreatic tissues. We determined the full-length sequence of a circRNA upregulated in PDAC, which was derived from two non-coding RNA loci on chromosome 12. The novel circRNA, named circPDAC RNA, was not expressed in normal human cells, but was expressed in PDAC and other carcinoma cells. The circPDAC RNA identified here might serve as a novel biomarker for cancers, including PDAC.

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義としては、環状RNAに特化したシークエンスによって膵癌という病態時に発現する環状RNAを網羅的に同定できた点が挙げられる。さらにこの環状RNAの全長配列を同定し、非コードRNAエクソンがバックスプライシングで生成されることを明らかにした。さらにこの環状RNAの生物学的機能を解析した。これらの検討は、環状RNAの研究を進めるうえでの基本的な戦略を示したことになる。いっぽう社会的には、この環状RNAが膵癌の新規のバイオマーカーになる可能性があり、臨床的に役立つ可能性が見込まれる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (14 results)

All 2022 2021 2020 2019

All Journal Article (12 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 12 results,  Open Access: 12 results) Presentation (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] HBx-induced degradation of Smc5/6 complex impairs homologous recombination-mediated repair of damaged DNA.2022

    • Author(s)
      Sekiba K, Otsuka M, Funato K, Miyakawa Y, Tanaka E, Seimiya T, Yamagami M, Tsutsumi T, Okushin K, Miyakawa K, Ryo A, Koike K.
    • Journal Title

      J Hepatol.

      Volume: 76 Issue: 1 Pages: 53-62

    • DOI

      10.1016/j.jhep.2021.08.010

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mutant KRAS drives metabolic reprogramming and autophagic flux in premalignant pancreatic cells.2021

    • Author(s)
      Suzuki T, Kishikawa T, Sato T, Takeda N, Sugiura Y, Seimiya T, Sekiba K, Ohno M, Iwata T, Ishibashi R, Otsuka M, Koike K.
    • Journal Title

      Cancer Gene Ther.

      Volume: - Issue: 5 Pages: 505-518

    • DOI

      10.1038/s41417-021-00326-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Humanized virus-suppressing factor inhibits hepatitis B virus infection by targeting viral cell entry2021

    • Author(s)
      Miyakawa Y, Otsuka M, Sekiba K, Funato K, Koike K.
    • Journal Title

      Heliyon .

      Volume: 14 Issue: 7 Pages: e07586-e07586

    • DOI

      10.1016/j.heliyon.2021.e07586

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential of HBx Gene for Hepatocarcinogenesis in Noncirrhotic Liver.2021

    • Author(s)
      Sekiba K, Otsuka M, Koike K
    • Journal Title

      Semin Liver Dis.

      Volume: 42 Issue: 02 Pages: 142-149

    • DOI

      10.1055/s-0041-1723033

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Emerging Roles of Exosomal Circular RNAs in Cancer2020

    • Author(s)
      Seimiya Takahiro、Otsuka Motoyuki、Iwata Takuma、Shibata Chikako、Tanaka Eri、Suzuki Tatsunori、Koike Kazuhiko
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 8 Pages: 568366-568366

    • DOI

      10.3389/fcell.2020.568366

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aberrant expression of a novel circular RNA in pancreatic cancer2020

    • Author(s)
      Seimiya Takahiro、Otsuka Motoyuki、Iwata Takuma、Tanaka Eri、Sekiba Kazuma、Shibata Chikako、Moriyama Masaru、Nakagawa Ryo、Maruyama Reo、Koike Kazuhiko
    • Journal Title

      Journal of Human Genetics

      Volume: 66 Issue: 2 Pages: 181-191

    • DOI

      10.1038/s10038-020-00826-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] HBx increases EGFR expression by inhibiting miR129?5p function2020

    • Author(s)
      Ochi Masanori、Otsuka Motoyuki、Maruyama Reo、Koike Kazuhiko
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 529 Issue: 2 Pages: 198-203

    • DOI

      10.1016/j.bbrc.2020.06.018

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identifying Inhibitors of the HBx-DDB1 Interaction Using a Split Luciferase Assay System2019

    • Author(s)
      Sekiba Kazuma、Otsuka Motoyuki、Koike Kazuhiko
    • Journal Title

      Journal of Visualized Experiments

      Volume: 154 Issue: 154

    • DOI

      10.3791/60652

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of circulating colorectal cancer cells by a custom microfluid system before and after endoscopic metallic stent placement2019

    • Author(s)
      REI ISHIBASHI, SHUNTARO YOSHIDA, NARIAKI ODAWARA, TAKAHIRO KISHIKAWA, RYO KONDO, AYAKO NAKADA, RYUNOSUKE HAKUTA, NAMINATSU TAKAHARA, ERI TANAKA, KAZUMA SEKIBA, TAKAHIRO SEIMIYA, TAKASHI OHNAGA, MOTOYUKI OTSUKA and KAZUHIKO KOIKE
    • Journal Title

      ONCOLOGY LETTERS

      Volume: 18 Pages: 6397-6404

    • DOI

      10.3892/ol.2019.11047

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of circular RNA CDR1?AS in colon cancer cells increases cell surface PD?L1 protein levels2019

    • Author(s)
      Tanaka Eri、Miyakawa Yu、Kishikawa Takahiro、Seimiya Takahiro、Iwata Takuma、Funato Kazuyoshi、Odawara Nariaki、Sekiba Kazuma、Yamagami Mari、Suzuki Tatsunori、Ishibashi Rei、Otsuka Motoyuki、Koike Kazuhiko
    • Journal Title

      Oncology Reports

      Volume: 42 Pages: 1459-1466

    • DOI

      10.3892/or.2019.7244

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pevonedistat, a Neuronal Precursor Cell-Expressed Developmentally Down-Regulated Protein 8-Activating Enzyme Inhibitor, Is a Potent Inhibitor of Hepatitis B Virus2019

    • Author(s)
      Sekiba Kazuma、Otsuka Motoyuki、Ohno Motoko、Yamagami Mari、Kishikawa Takahiro、Seimiya Takahiro、Suzuki Tatsunori、Tanaka Eri、Ishibashi Rei、Funato Kazuyoshi、Koike Kazuhiko
    • Journal Title

      Hepatology

      Volume: in press Issue: 5 Pages: 1903-1915

    • DOI

      10.1002/hep.30491

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of HBV Transcription From cccDNA With Nitazoxanide by Targeting the HBx?DDB1 Interaction2019

    • Author(s)
      Sekiba Kazuma、Otsuka Motoyuki、Ohno Motoko、Yamagami Mari、Kishikawa Takahiro、Suzuki Tatsunori、Ishibashi Rei、Seimiya Takahiro、Tanaka Eri、Koike Kazuhiko
    • Journal Title

      Cellular and Molecular Gastroenterology and Hepatology

      Volume: 7 Issue: 2 Pages: 297-312

    • DOI

      10.1016/j.jcmgh.2018.10.010

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 膵癌で高発現する新規環状 RNA の同定とバイオマーカー応用2021

    • Author(s)
      清宮崇博、大塚基之、小池和彦
    • Organizer
      第107回日本消化器病学会総会
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] Abberant expression of novel circular RNA in pancreatic cancer2020

    • Inventor(s)
      Seimiya T, Otsuka M, Koiek K.
    • Industrial Property Rights Holder
      Seimiya T, Otsuka M, Koiek K.
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
    • Overseas

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Published: 2019-04-18   Modified: 2023-01-30  

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