Analyses of liver-specific miRNA function and the development of the strategy about the efficient induction of differentiation into hepatocytes

• Project/Area Number: 22590718
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: KONDO Yuuji 東京大学, 医学部附属病院, 助教 (00572231)
• Co-Investigator(Kenkyū-buntansha): 吉田 晴彦 東京大学, 医学部附属病院, 講師 (60240305) ; 大塚 基之 東京大学, 医学部附属病院, 助教 (90518945)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 肝臓学 / microRNA / 分化 / 肝細胞 / 肝癌 / AFP / microRNA122 / 癌幹細胞 / 肝細胞癌

Research Abstract

Liver specific miR122 is frequently downregulated in hepatocellular carcinoma (HCC). Knockdown of miR122 induces AFP expression, indicating the de-differentiation of hepatocytes. Decreased miR122 expression leads to the increased expression of CUX1, a transcriptional factor, which is related with the aggressiveness of HCC. From these results, decreased miR122 results in the AFP expression and aggressiveness of HCC, which is a molecular explanation about the clinical poor prognosis of HCCs with high AFP expression.

Research Products

• [Journal Article] Systemic combination therapy of intravenous continuous 5-fluorouracil and subcutaneous pegylated interferon alfa-2a for advanced hepatocellular carcinoma. (2012)
  • Author(s): Kondo Y et al. (19人中13番目)
  • Journal Title: J Gastroenterol. Volume: 47 Issue: 10 Pages: 1152-9
  • DOI: 10.1007/s00535-012-0574-3
  • NAID: 10031122104
  • Peer Reviewed
• [Journal Article] Radiofrequency ablation for hepatocellular carcinoma: 10-year outcome and prognostic factors. (2012)
  • Author(s): Kondo Y et al. (14人中10番目)
  • Journal Title: Am J Gastroenterol. Volume: 107 Issue: 4 Pages: 569-77
  • DOI: 10.1038/ajg.2011.425
  • Peer Reviewed
• [Journal Article] Evaluation of molecular targeted cancer drug by changes in tumor marker doubling times. (2012)
  • Author(s): Kondo Y et al. (10人中4番目)
  • Journal Title: J Gastroenterol. Volume: 47 Issue: 1 Pages: 71-8
  • DOI: 10.1007/s00535-011-0462-2
  • NAID: 10030295766
  • Peer Reviewed
• [Journal Article] MicroRNA122 is a key regulator of alpha-fetoprotein expression and influences the aggressiveness of hepatocellular carcinoma. (2011)
  • Author(s): Kojima K, Takata A, Vadnais C, Otsuka M, Yoshikawa T, Akanuma M, Kondo Y, Kang YJ, Kishikawa T, Kato N, Xie Z, Zhang WJ, Yoshida H,Omata M, Nepveu A, Koike K.
  • Journal Title: Nat Commun Volume: 2 Pages: 338-338
  • Peer Reviewed
• [Journal Article] Intrahepatic bile ductdilatation after percutaneous radiofrequency ablation for hepatocellular carcinoma: impact on patient's prognosis. (2011)
  • Author(s): Kondo Y, Shiina S, Tateishi R, Arano T, Uchino K, Enooku K, Goto E, Nakagawa H, Masuzaki R, Asaoka Y, Fujie H, Goto T, Omata M, Yoshida H, Koike K.
  • Journal Title: Liver Int Volume: 31 Pages: 197-205
  • Peer Reviewed
• [Journal Article] MicroRNA122 is a key regulator of alpha-fetoprotein expression and influences the aggressiveness of hepatocellular carcinoma (2011)
  • Author(s): Kojima K, Takata A, Vadnais C, Otsuka M, Yoshikawa T, Akanuma M, Kondo Y, Kang YJ, Kishikawa T, Kato N, Xie Z, Zhang WJ, Yoshida H, Omata M, Nepveu A, Koike K
  • Journal Title: Nat Commun. Volume: 2 Issue: 1 Pages: 338-338
  • DOI: 10.1038/ncomms1345
  • Peer Reviewed
• [Journal Article] Intrahepatic bile duct dilatation after percutaneous radiofrequency ablation for hepatocellular carcinoma: impact on patient's prognosis. (2011)
  • Author(s): Kondo Y, Shiina S, Tateishi R, Arano T, Uchino K, Enooku K, Goto E, Nakagawa H, Masuzaki R, Asaoka Y, Fujie H, Goto T, Omata M, Yoshida H, Koike K.
  • Journal Title: Liver Int Volume: 31(2) Issue: 2 Pages: 197-205
  • DOI: 10.1111/j.1478-3231.2010.02415.x
  • Peer Reviewed
• [Journal Article] Prediction of hepatocellular carcinoma development by plasma ADAMTS 13 in chronic hepatitis B and C (2011)
  • Author(s): Ikeda H, Tateishi R, Enooku K, Yoshida H, nakagawa H, Masuzaki R, Kondo Y, Goto T, Shiina S, Kume Y, Tomiya T, Inoue Y, Nishikawa T, Ohtomo N, Tanoue Y, Ono T, Koike K, Yatomi Y
  • Journal Title: Cancer Epidemiol Biomarkers Prev. Volume: 20 Issue: 10 Pages: 2204-11
  • DOI: 10.1158/1055-9965.epi-11-0464
  • Peer Reviewed
• [Journal Article] Serum level of adiponectin and the risk of liver cancer development in chronic hepatitis C patients. (2011)
  • Author(s): Arano T, Nakagawa H, Tateishi R, Ikeda H, Uchino K, Enooku K, Goto E, Masuzaki R, Asaoka Y, Kondo Y, Goto T, Shiina S, Omata M, Yoshida H, Koike K.
  • Journal Title: Int J Cancer. Volume: (In press)(掲載確定)
  • Peer Reviewed
• [Journal Article] Intrahepatic bile duct dilatation after percutaneous radiofrequency ablation for hepatocellular carcinoma : impact on patient's prognosis. (2011)
  • Author(s): Koncro Y, Shiina S, Tateishi R, Arano T, Uchino K, Enooku K, Goto E, Nakagawa H, Masuzaki R, Asaoka Y, Fujie H, Goto T, Omata M, Yoshida H, Koike K.
  • Journal Title: Liver Int. Volume: (In press)(掲載確定) Pages: 197-205
  • Peer Reviewed
• [Journal Article] A phise I/II trial of the oral antiangiogenic agent TSU-68 in patients with advanced hepatocellular carcinoma. (2011)
  • Author(s): Kanai F, Yoshida H, Tateishi R, Sato S, Kawabe T, Obi S, Kondo Y, Taniguchi M, Tagawa K, Ikeda M, Morizane C, Okusaka T, Arioka H, Shiina S, Omata M.
  • Journal Title: Cancer Chemother Pharmacol. Volume: (In press)(掲載確定) Pages: 315-24
  • Peer Reviewed
• [Presentation] 経皮的ラジオ波焼灼術の安全性と合併症対策 (2012)
  • Author(s): 近藤祐嗣
  • Organizer: 第48回日本肝臓学会総会
  • Place of Presentation: 石川県立音楽堂
  • Year and Date: 2012-06-08
• [Presentation] 経皮的ラジオ波焼灼術の安全性と合併症対策
  • Author(s): 近藤祐嗣
  • Organizer: 第48 回日本肝臓学会総会
  • Place of Presentation: 石川県立音楽
• [Remarks]
  • URL: https://sites.google.com/site/225kenncrna/
• [Remarks] 研究内容成果に関するwebページ
  • URL: https://sites.google.com/site/225kenncrna/
• [Remarks]
  • URL: https://sites.google.com/site/225kenncrna/
• [Remarks]
  • URL: http://gastro.m.u-tokyo.ac.jp/med/home.html