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Oncotarget. 2015 May 30;6(15):13658-70.

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

Author information

1
Department of Pathology and State Key Laboratory for Liver Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
2
Department of Physics and Department of Biology, Centre for Quantitative Systems Biology, Hong Kong Baptist University, Hong Kong, China.
3
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

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.

KEYWORDS:

Rho/ROCK signaling pathway; cancer metastasis; cytoskeletal reorganization; hepatocellular carcinoma; miR-200 family

PMID:
25909223
PMCID:
PMC4537040
DOI:
10.18632/oncotarget.3700
[Indexed for MEDLINE]
Free PMC Article
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