Department of Physics; Department of Biology
MiR-200 family is an important regulator of epithelial-mesenchymal transition and has been implicated in human carcinogenesis. However, their expression and functions in human cancers remain controversial. In the work presented here, we showed that miR-200 family members were frequently down-regulated in hepatocellular carcinoma (HCC). Although all five members of miR-200 family inhibited ZEB1/2 expression in HCC cell lines, we showed that overexpression only of the miR-200b/200c/429 subfamily, but not the miR-200a/141 subfamily, resulted in impeded HCC cell migration. Further investigations led to the identification of RhoA and ROCK2 as specific down-stream targets of the miR-200b/200c/429 subfamily. We demonstrated that the miR-200b/200c/429 subfamily inhibited HCC cell migration through modulating Rho/ROCK mediated cell cytoskeletal reorganization and cell-substratum adhesion. Re-expression of miR-200b significantly suppressed lung metastasis of HCC cells in an orthotopic liver implantation model in vivo. In conclusion, our findings identified the miR-200b/200c/429 subfamily as metastasis suppressor microRNAs in human HCC and highlighted the functional discrepancy among miR-200 family members.
hepatocellular carcinoma, miR-200 family, cytoskeletal reorganization, Rho/ROCK signaling pathway, cancer metastasis
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Wong, Chun-Ming, Lai Wei, Sandy Leung-Kuen Au, Dorothy Ngo-Yin Fan, Yuan Zhou, Felice Ho-Ching Tsang, Cheuk-Ting Law, Joyce Man-Fong Lee, Xianghuo He, Jue Shi, Carmen Chak-Lui Wong, and Irene Oi-Lin Ng. "MiR-200b/200c/429 subfamily negatively regulates Rho/ROCK signaling pathway to suppress hepatocellular carcinoma metastasis." Oncotarget 6.15 (2015): 13658-13670.