MiR-200b/200c/429 subfamily negatively regulates Rho/ ROCK signaling pathway to suppress hepatocellular carcinoma metastasis

Chun Ming Wong*, 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, Irene Oi Lin Ng

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

74 Citations (Scopus)
26 Downloads (Pure)


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 cellsubstratum 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.

Original languageEnglish
Pages (from-to)13658-13670
Number of pages13
Issue number15
Publication statusPublished - 2015

Scopus Subject Areas

  • Oncology

User-Defined Keywords

  • Cancer metastasis
  • Cytoskeletal reorganization
  • Hepatocellular carcinoma
  • mir-200 family
  • RHO/ROCK signaling pathway


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