Research Abstract



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

2011年6月7日 Nature Communications 2 : 338 doi: 10.1038/ncomms1345


小島 健太郎1*,高田 朱弥1*,Charles Vadnais2*,大塚 基之1,吉川 剛史1,赤沼 真夫3,近藤 祐嗣1,Young Jun Kang4,岸川 孝弘1,加藤 直也5,Zhifang Xie6,Weiping J. Zhang6,吉田 晴彦1,小俣 政男1,Alain Nepveu2 & 小池 和彦2

  1. 東京大学医学系研究科消化器内科
  2. マギル大学(カナダ)
  3. 公益財団法人 朝日生命成人病研究所
  4. スクリプス研究所(米国)
  5. 東京大学 医科学研究所
  6. 第二軍医大学(中国)
    *These authors contributed equally to this work.
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.