TY - JOUR
T1 - MiR-200b/200c/429 subfamily negatively regulates Rho/ ROCK signaling pathway to suppress hepatocellular carcinoma metastasis
AU - Wong, Chun Ming
AU - Wei, Lai
AU - Au, Sandy Leung Kuen
AU - Fan, Dorothy Ngo Yin
AU - Zhou, Yuan
AU - Tsang, Felice Ho Ching
AU - Law, Cheuk Ting
AU - Lee, Joyce Man Fong
AU - He, Xianghuo
AU - Shi, Jue
AU - Wong, Carmen Chak Lui
AU - Ng, Irene Oi Lin
N1 - The study was supported by Hong Kong Research Grants Council Collaborative Research Fund (HKU 1/06C
and HKU 7/CRG/09), General Research Fund (HKU 775811 and HKU 782411), SK Yee Medical Research Fund 2011, and Lee Shiu Family Foundation.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Cancer metastasis
KW - Cytoskeletal reorganization
KW - Hepatocellular carcinoma
KW - mir-200 family
KW - RHO/ROCK signaling pathway
UR - https://www.scopus.com/pages/publications/84931075204
U2 - 10.18632/oncotarget.3700
DO - 10.18632/oncotarget.3700
M3 - Journal article
C2 - 25909223
AN - SCOPUS:84931075204
SN - 1949-2553
VL - 6
SP - 13658
EP - 13670
JO - Oncotarget
JF - Oncotarget
IS - 15
ER -
