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MicroRNA122 is a key regulator of α-fetoprotein expression and influences the aggressiveness of hepatocellular carcinoma

Author

Listed:
  • Kentaro Kojima

    (Graduate School of Medicine, The University of Tokyo)

  • Akemi Takata

    (Graduate School of Medicine, The University of Tokyo)

  • Charles Vadnais

    (Biochemistry and Medicine, McGill University)

  • Motoyuki Otsuka

    (Graduate School of Medicine, The University of Tokyo)

  • Takeshi Yoshikawa

    (Graduate School of Medicine, The University of Tokyo)

  • Masao Akanuma

    (The Institute for Adult Diseases, Asahi Life Foundation)

  • Yuji Kondo

    (Graduate School of Medicine, The University of Tokyo)

  • Young Jun Kang

    (The Scripps Research Institute)

  • Takahiro Kishikawa

    (Graduate School of Medicine, The University of Tokyo)

  • Naoya Kato

    (Unit of Disease Control Genome Medicine, The Institute of Medical Science, The University of Tokyo)

  • Zhifang Xie

    (Second Military Medical University)

  • Weiping J. Zhang

    (Second Military Medical University)

  • Haruhiko Yoshida

    (Graduate School of Medicine, The University of Tokyo)

  • Masao Omata

    (Graduate School of Medicine, The University of Tokyo)

  • Alain Nepveu

    (Biochemistry and Medicine, McGill University)

  • Kazuhiko Koike

    (Graduate School of Medicine, The University of Tokyo)

Abstract

α-fetoprotein (AFP) is not only a widely used biomarker in hepatocellular carcinoma (HCC) surveillance, but is also clinically recognized as linked with aggressive tumour behaviour. Here we show that deregulation of microRNA122, a liver-specific microRNA, is a cause of both AFP elevation and a more biologically aggressive phenotype in HCC. We identify CUX1, a direct target of microRNA122, as a common central mediator of these two effects. Using liver tissues from transgenic mice in which microRNA122 is functionally silenced, an orthotopic xenograft tumour model, and human clinical samples, we further demonstrate that a microRNA122/CUX1/microRNA214/ZBTB20 pathway regulates AFP expression. We also show that the microRNA122/CUX1/RhoA pathway regulates the aggressive characteristics of tumours. We conclude that microRNA122 and associated signalling proteins may represent viable therapeutic targets, and that serum AFP levels in HCC patients may be a surrogate marker for deregulated intracellular microRNA122 signalling pathways in HCC tissues.

Suggested Citation

  • Kentaro Kojima & Akemi Takata & Charles Vadnais & Motoyuki Otsuka & Takeshi Yoshikawa & Masao Akanuma & Yuji Kondo & Young Jun Kang & Takahiro Kishikawa & Naoya Kato & Zhifang Xie & Weiping J. Zhang &, 2011. "MicroRNA122 is a key regulator of α-fetoprotein expression and influences the aggressiveness of hepatocellular carcinoma," Nature Communications, Nature, vol. 2(1), pages 1-11, September.
    • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1345
    DOI: 10.1038/ncomms1345
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    Cited by:

    1. Sung Kyu Song & Woon Yong Jung & Seung-Keun Park & Chul-Woon Chung & Yongkeun Park, 2019. "Significantly different expression levels of microRNAs associated with vascular invasion in hepatocellular carcinoma and their prognostic significance after surgical resection," PLOS ONE, Public Library of Science, vol. 14(9), pages 1-15, September.

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