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Gain of miR-151 on chromosome 8q24.3 facilitates tumour cell migration and spreading through downregulating RhoGDIA

Nature Cell Biology volume 12, pages 390399 (2010) | Download Citation

Abstract

Recurrent chromosomal aberrations are often observed in hepatocellular carcinoma (HCC), but little is known about the functional non-coding sequences, particularly microRNAs (miRNAs), at the chromosomal breakpoints in HCC. Here we show that 22 miRNAs are often amplified or deleted in HCC. MicroRNA-151 (miR-151), a frequently amplified miRNA on 8q24.3, is correlated with intrahepatic metastasis of HCC. We further show that miR-151, which is often expressed together with its host gene FAK, encoding focal adhesion kinase, significantly increases HCC cell migration and invasion in vitro and in vivo, mainly through miR-151-5p, but not through miR-151-3p. Moreover, miR-151 exerts this function by directly targeting RhoGDIA, a putative metastasis suppressor in HCC, thus leading to the activation of Rac1, Cdc42 and Rho GTPases. In addition, miR-151 can function synergistically with FAK to enhance HCC cell motility and spreading. Thus, our findings indicate that chromosome gain of miR-151 is a crucial stimulus for tumour invasion and metastasis of HCC.

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Acknowledgements

We thank Didier Trono (School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland) for providing the pWPXL, psPAX2 and pMD2.G plasmids. This work was supported by grants from the Science and Technology Commission of Shanghai Municipality (07DJ14006), the Ministry of Human Resources and Social Security of China (2007-170), and the Ministry of Health of China (2008ZX10002-017).

Author information

Author notes

    • Jie Ding
    •  & Shenglin Huang

    These authors contributed equally to this work.

Affiliations

  1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.

    • Jie Ding
    • , Shenglin Huang
    • , Shunquan Wu
    • , Yingjun Zhao
    • , Linhui Liang
    • , Chao Ge
    • , Jian Yao
    • , Dafang Wan
    • , Hongyang Wang
    • , Jianren Gu
    • , Jinjun Li
    • , Hong Tu
    •  & Xianghuo He
  2. Shanghai Medical College, Fudan University, Shanghai 200032, China.

    • Yingjun Zhao
    •  & Jian Yao
  3. Department of Experimental Pathology, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.

    • Mingxia Yan
    •  & Ming Yao
  4. Qi Dong Liver Cancer Institute, Qi Dong, Jiangsu 226200, China.

    • Taoyang Chen

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Contributions

X.H., S.H., H.T. and D.W. planned the experimental design. J.D., S.H., S.W., Y.Z., L.L., M.-X.Y., C.G., J.Y., T.C., M.Y. and J.L. conducted the experiments. J.D., S.H. and X.H. analysed data. X.H., S.H., J.D., H.W. and J.G. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Xianghuo He.

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https://doi.org/10.1038/ncb2039

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