• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Post-translational Modifications of RNA-binding Proteins in obesity-associated colorectal carcinogenesis

Research Project

Project/Area Number 20K08350
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionYamagata University

Principal Investigator

Sasaki Yu  山形大学, 医学部, 講師 (60466620)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords大腸癌 / 大腸腺腫 / 肥満 / 代謝 / メタボリックシンドローム / インスリン抵抗性 / RNA修飾 / HuR / RNA転写後調節 / RNAシークエンス / 大腸がん / GIP / インクレチン / 大腸発がん
Outline of Research at the Start

本邦をはじめ世界的な大腸癌増加の主な要因として肥満、メタボリックシンドロームの増加がある。この病態の中核にはインスリン抵抗性やアディポサイトカイン分泌異常、慢性低炎症状態があるが、このような変調がどのように大腸癌を引き起こすのか、その分子機序は不明な点が多い。
本研究ではRNA結合蛋白HuRに着目し、肥満関連大腸がんにおいて、代謝異常と関連したHuRの細胞内局在の変化、標的mRNAの同定とその安定性について明らかにする。これにより、肥満、代謝異常からの大腸発がんにおける、HuRによるRNAの転写後調節を介した発がん機序を明らかにし、それに基づいた予防や治療を可能とする新しい分子基盤を創出する。

Outline of Final Research Achievements

The expression of HuR in the cytoplasm exhibited an increase in colorectal cancers among individuals with obesity. Additionally, in colon cancer cell lines, insulin induced the translocation of HuR from the nucleus to the cytoplasm and significantly augmented the mRNA binding to HuR by at least a fourfold increase. Through a comprehensive transcriptome analysis, I identified 38 mRNAs with a more than twofold enhanced binding affinity to HuR. Notably, the X gene, which displayed the most substantial decrease in binding, experienced a 50% reduction in mRNA stability. Intriguingly, knockout mice lacking this gene exhibited lymphoma-like tumor growth in the small intestine. Further investigation will elucidate the precise mechanism by which HuR-mediated post-transcriptional regulation of RNA contributes to colon carcinogenesis. Moreover, these findings will lay the foundation for developing novel molecular strategies to effectively prevent and treat colon cancer.

Academic Significance and Societal Importance of the Research Achievements

本研究では、肥満関連大腸癌におけるRNA結合蛋白HuRの核細胞質移行や標的mRNAsの変化、および大腸癌の発育進展に関わる可能性のある新規の標的遺伝子を明らかにしました。代謝変化によるHuRを介したRNA転写後制御の変調が肥満関連大腸発癌を導くという新しい機序を解明し、それを制御する方策を見出すことで、世界的に増えている肥満関連大腸癌の征圧につなげることが期待できます。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (20 results)

All 2023 2022 2021 2020

All Journal Article (9 results) (of which Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (11 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Modulation of AMPK/ TET2/ 5-hmC axis in response to metabolic alterations as a novel pathway for obesity-related colorectal cancer development2023

    • Author(s)
      Kon Takashi、Sasaki Yu、Abe Yasuhiko、Onozato Yusuke、Yagi Makoto、Mizumoto Naoko、Sakai Takayuki、Umehara Matsuki、Ito Minami、Nakamura Shuhei、Goto Hiroki、Ueno Yoshiyuki
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 2858-2858

    • DOI

      10.1038/s41598-023-29958-2

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Low serum pancreatic amylase levels as a novel latent risk factor for colorectal adenoma in non‐alcohol drinkers2022

    • Author(s)
      Sasaki Yu、Abe Yasuhiko、Nishise Shoichi、Yagi Makoto、Mizumoto Naoko、Kon Takashi、Onozato Yusuke、Sakai Takayuki、Umehara Matsuki、Ito Minami、Ueno Yoshiyuki
    • Journal Title

      Journal of Gastroenterology and Hepatology

      Volume: 37 Issue: 4 Pages: 660-668

    • DOI

      10.1111/jgh.15748

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reply: Serum pancreatic amylase and colorectal adenoma: From clinical research to practice2022

    • Author(s)
      Sasaki Y、Abe Y、Nishise S、Ueno Y
    • Journal Title

      Journal of Gastroenterology and Hepatology

      Volume: 37 Issue: 11 Pages: 2189-2190

    • DOI

      10.1111/jgh.15993

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tu1543: CHARACTERISTICS OF THE GUT MICROBIOTA IN VISCERALLY OBESE PATIENTS WITH COLORECTAL ADENOMA2022

    • Author(s)
      Sakai Takayuki、Sasaki Yu、Abe Yasuhiko、Nishise Shoichi、Sato Hidenori、Onozato Yusuke、Kon Takashi、Yagi Makoto、Mizumoto Naoko、Ito Minami、Umehara Matsuki、Nakamura Shuhei、Tsuchida Hidemoto、Goto Hiroki、Koseki Ayumi、Ueno Yoshiyuki
    • Journal Title

      Gastroenterology

      Volume: 162 Issue: 7 Pages: S-1003-S-1004

    • DOI

      10.1016/s0016-5085(22)62381-3

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mo1108: A NOVEL HUR TARGET-THE ABTB1 GENE-IS INVOLVED IN A POTENTIAL MECHANISM OF OBESITY-RELATED COLORECTAL CARCINOGENESIS2022

    • Author(s)
      Sasaki Yu、Abe Yasuhiko、Kon Takashi、Sato Hidenori、Onozato Yusuke、Yagi Makoto、Mizumoto Naoko、Sakai Takayuki、Ito Minami、Umehara Matsuki、Nakamura Shuhei、Tsuchida Hidemoto、Goto Hiroki、Koseki Ayumi、Ueno Yoshiyuki
    • Journal Title

      Gastroenterology

      Volume: 162 Issue: 7 Pages: S-701

    • DOI

      10.1016/s0016-5085(22)61641-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 大腸がんの発生・進展と腸内細菌の関わり2022

    • Author(s)
      佐々木悠,阿部靖彦,東海林正邦,堺貴之,上野義之
    • Journal Title

      Progress in Medicine

      Volume: 42 Pages: 47-52

    • Related Report
      2021 Research-status Report
  • [Journal Article] Characteristics of the gut microbiome profile in obese patients with colorectal cancer2021

    • Author(s)
      Shoji Masakuni、Sasaki Yu、Abe Yasuhiko、Nishise Shoichi、Yaoita Takao、Yagi Makoto、Mizumoto Naoko、Kon Takashi、Onozato Yusuke、Sakai Takayuki、Umehara Matsuki、Ito Minami、Koseki Ayumi、Murakami Ryoko、Miyano Yuki、Sato Hidenori、Ueno Yoshiyuki
    • Journal Title

      JGH Open

      Volume: 5 Issue: 4 Pages: 498-507

    • DOI

      10.1002/jgh3.12529

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Insulin and glucose altered AMPK-TET2-5hmC axix toward on the obesity-related colorectal cancer development2021

    • Author(s)
      Takashi Kon, Yu Sasaki, Yasuhiko Abe, Yusuke Onozato, Makoto Yagi, Naoko Mizumoto, Takayuki Sakai, Matsuki Umehara, Minami Ito, Ayumi Koseki, Yoshiyuki Ueno
    • Journal Title

      Gastroenterology

      Volume: 160

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] 肥満、メタボリックシンドロームと消化管病態の関連性2020

    • Author(s)
      佐々木悠,阿部靖彦,八木周,水本尚子,今孝志,小野里祐介,堺貴之,梅原松樹,伊藤南,上野義之
    • Journal Title

      消化器・肝臓内科

      Volume: 8 Pages: 341-348

    • Related Report
      2020 Research-status Report
  • [Presentation] 新たな大腸腺腫のリスク因子:血清膵アミラーゼ値の低下~大腸腺腫患者における非アルコール性脂肪肝・膵の解析~2022

    • Author(s)
      佐々木悠、阿部靖彦、上野義之
    • Organizer
      第108回日本消化器病学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 肥満関連大腸がんにおけるTET2遺伝子発現の検討2021

    • Author(s)
      今孝志,佐々木悠,阿部靖彦,小野里祐介,八木周,水本尚子,堺貴之,伊藤南,梅原松樹,小関歩,上野義之
    • Organizer
      第107回日本消化器病学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 肥満関連大腸癌における腸内細菌叢の解析2021

    • Author(s)
      東海林正邦,佐々木悠,阿部靖彦,矢尾板孝夫,八木周,水本尚子,小野里祐介,今孝志,堺貴之,伊藤南,梅原松樹,佐藤秀則,西瀬祥一,上野義之
    • Organizer
      第107回日本消化器病学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 若年発症大腸癌(EOCRC)の臨床的特徴の検討2021

    • Author(s)
      梅原松樹,佐々木悠,阿部靖彦, 八木周, 水本尚子, 小野里祐介, 今孝志, 堺貴之, 伊藤南, 上野義之
    • Organizer
      第63回日本消化器病学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 大腸腺腫患者における腸内細菌叢の解析2021

    • Author(s)
      堺貴之,佐々木悠,阿部靖彦, 西瀬祥一, 東海林正邦, 八木周, 水本尚子, 小野里祐介, 今孝志, 梅原松樹, 伊藤南, 上野 義之
    • Organizer
      第63回日本消化器病学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Ectopic fat accumulation in the liver and pancreas in patients with colorectal adenoma2020

    • Author(s)
      Yu Sasaki, Yasuhiko Abe, Shoichi Nishise, Takao Yaoita, Makoto Yagi, Naoko Mizumoto, Masakuni Shoji, Yusuke Onozato, Takashi Kon, Takayuki Sakai, Yoshiyuki Ueno
    • Organizer
      American Gastroenterological Association, DDW2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Changes in the gut microbiota and their effect on pathogenesis in obese patients with colorectal cancer2020

    • Author(s)
      Masakuni Shoji, Yu Sasaki, Yasuhiko Abe, Shoichi Nishise, Takao Yaoita, Makoto Yagi, Naoko Mizumoto, Yusuke Onozato, Takashi Kon, Takayuki Sakai, Ayumi Koseki, Hidenori Sato, Yoshiyuki Ueno
    • Organizer
      American Gastroenterological Association, DDW2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Obesity and colorectal neoplasm: identifying obesity-associated somatic genomic signals from colorectal adenoma and carcinoma2020

    • Author(s)
      Takashi Kon, Yu Sasaki, Yasuhiko Abe, Takao Yaoita, Makoto Yagi, Naoko Mizumoto, Masakuni Shoji, Yusuke Onozato, Takayuki Sakai, Ayumi Koseki, Hidenori Sato, Yoshiyuki Ueno
    • Organizer
      American Gastroenterological Association, DDW2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 大腸癌患者における腸内細菌叢と肥満・代謝異常との関連性2020

    • Author(s)
      東海林正邦,佐々木悠,上野義之
    • Organizer
      第106回日本消化器病学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 早期胃癌の異時性再発を予測する分子マーカーの同定2020

    • Author(s)
      佐々木悠,阿部靖彦,上野義之
    • Organizer
      第106回日本消化器病学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 肥満関連大腸腫瘍における遺伝子変化の特徴についての検討2020

    • Author(s)
      今孝志,佐々木悠,阿部靖彦,小野里祐介,佐藤秀則,矢尾板孝夫,八木周,水本尚子,東海林正邦,堺貴之,小関歩,上野義之
    • Organizer
      第62回日本消化器病学会大会
    • Related Report
      2020 Research-status Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi