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Epithelial-mesenchymal transition and autophagy of hepatoma cells by the microenvironment change

Research Project

Project/Area Number 24590983
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionNagasaki University

Principal Investigator

NAKAO Kazuhiko  長崎大学, 医歯薬学総合研究科(医学系), 教授 (00264218)

Co-Investigator(Kenkyū-buntansha) MIYAAKI Hisamitsu  長崎大学, 病院(医学系), 助教 (20437891)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords肝癌細胞 / インスリン / 分岐鎖アミノ酸 / VEGF / 上皮間葉移行 / 微小環境変化 / microRNA-122
Outline of Final Research Achievements

We analyzed the expression of vascular endothelial growth factor (VEGF) in human hepatomacells under high-insulin culture conditions, and examined the effect of branched-chain amino acid (BCAA) on VEGF expression. VEGF secretion was significantly increased by 200 nM of insulin under BCAA deficient conditions, but it was repressed by the addition of BCAA. BCAA activated the mTOR pathway and increase HIF-1α expression under high-insulin culture conditions, however quantitative PCR analysis showed that insulin-induced expression of VEGF mRNAs decreased 2 h after the addition of BCAA. The half-lives of VEGF mRNAs were shortened in the presence of BCAA compared to the absence of BCAA. Therefore it is thought that BCAA regulate VEGF expression mainly at the post-transcriptional level. All three BCAA components(valine, Leucine, and Isoleucine) were required for acceleration of insulin-induced VEGF mRNA degradation.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (3 results)

All 2015 2014 2012

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results)

  • [Journal Article] Significance of miRNA-122 in chronic hepatitis C patients with serotype 1 on interferon therapy.2015

    • Author(s)
      Kamo Y, Ichikawa T, Miyaaki H, Uchida S, Yamaguchi T, Shibata H, Honda T, Taura N, Isomoto H, Takeshima F, Nakao K.
    • Journal Title

      Hepatol Res.

      Volume: 45(1) Issue: 1 Pages: 88-96

    • DOI

      10.1111/hepr.12317

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Antitumor function of microRNA-122 against hepatocellular carcinoma.2014

    • Author(s)
      Nakao K, Miyaaki H, Ichikawa T.
    • Journal Title

      J Gastroenterol.

      Volume: 49(4) Issue: 4 Pages: 589-93

    • DOI

      10.1007/s00535-014-0932-4

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Branched-chain amino acid deficiency stabilizes insulin-induced vascular2012

    • Author(s)
      Miuma S, Ichikawa T, Arima K, Takeshita S, Muraoka T, Matsuzaki T, Ootani M,
    • Journal Title

      J Cell Biochem.

      Volume: 113 Issue: 10 Pages: 3113-3121

    • DOI

      10.1002/jcb.24188

    • Related Report
      2012 Research-status Report
    • Peer Reviewed

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Published: 2013-05-31   Modified: 2019-07-29  

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