Document Type

Journal Article

Department/Unit

Department of Physics; Department of Biology

Language

English

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

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

Publication Date

3-2015

Source Publication Title

Oncotarget

Volume

6

Issue

15

Start Page

13658

End Page

13670

Publisher

Impact Journals

Peer Reviewed

1

Copyright

This article is licensed under a Creative Commons Attribution License

DOI

10.18632/oncotarget.3700

Link to Publisher's Edition

http://dx.doi.org/10.18632/oncotarget.3700

ISSN (electronic)

2084882X

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