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).
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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.
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Ding, J., Huang, S., Wu, S. et al. Gain of miR-151 on chromosome 8q24.3 facilitates tumour cell migration and spreading through downregulating RhoGDIA. Nat Cell Biol 12, 390–399 (2010). https://doi.org/10.1038/ncb2039
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DOI: https://doi.org/10.1038/ncb2039
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