Author: ["Jie Ding","Shenglin Huang","Shunquan Wu","Yingjun Zhao","Linhui Liang","Mingxia Yan","Chao Ge","Jian Yao","Taoyang Chen","Dafang Wan","Hongyang Wang","Jianren Gu","Ming Yao","Jinjun Li","Hong Tu","Xianghuo He"]
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Abstract
Twenty-two microRNAs are found to be amplified or deleted in hepatocellular carcinoma (HCC). miR-151 is encoded by an intron in the focal adhesion kinase FAK-1 gene, with which it is co-transcribed, and increases HCC cell migration in vitro and invasion in vivo by directly targeting RhoGDIA. miR-151 amplification correlates with HCC metastasis. 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.Cite this article
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 