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

TitleMiR-200b/200c/429 subfamily negatively regulates Rho/ROCK signaling pathway to suppress hepatocellular carcinoma metastasis
Authors
Issue Date2015
PublisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html
Citation
Oncotarget, 2015, v. 6 n. 15, p. 13658-13670 How to Cite?
AbstractMiR-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.
Persistent Identifierhttp://hdl.handle.net/10722/214731
ISSN
2015 Impact Factor: 5.008
2015 SCImago Journal Rankings: 2.294
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorWong, CM-
dc.contributor.authorWei, L-
dc.contributor.authorAu, SLK-
dc.contributor.authorFan, DNY-
dc.contributor.authorZhou, Y-
dc.contributor.authorTsang, FHC-
dc.contributor.authorLaw, CT-
dc.contributor.authorLee, JMF-
dc.contributor.authorHe, X-
dc.contributor.authorShi, J-
dc.contributor.authorWong, CCL-
dc.contributor.authorNg, IOL-
dc.date.accessioned2015-08-21T11:53:23Z-
dc.date.available2015-08-21T11:53:23Z-
dc.date.issued2015-
dc.identifier.citationOncotarget, 2015, v. 6 n. 15, p. 13658-13670-
dc.identifier.issn1949-2553-
dc.identifier.urihttp://hdl.handle.net/10722/214731-
dc.description.abstractMiR-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.-
dc.languageeng-
dc.publisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html-
dc.relation.ispartofOncotarget-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleMiR-200b/200c/429 subfamily negatively regulates Rho/ROCK signaling pathway to suppress hepatocellular carcinoma metastasis-
dc.typeArticle-
dc.identifier.emailWong, CM: jcmwong@hkucc.hku.hk-
dc.identifier.emailTsang, FHC: fhtsang@hku.hk-
dc.identifier.emailLee, JMF: joyce@pathology.hku.hk-
dc.identifier.emailWong, CCL: carmencl@pathology.hku.hk-
dc.identifier.emailNg, IOL: iolng@hku.hk-
dc.identifier.authorityWong, CM=rp00231-
dc.identifier.authorityWong, CCL=rp01602-
dc.identifier.authorityNg, IOL=rp00335-
dc.description.naturepublished_or_final_version-
dc.identifier.pmid25909223-
dc.identifier.pmcidPMC4537040-
dc.identifier.hkuros247222-
dc.identifier.volume6-
dc.identifier.issue15-
dc.identifier.spage13658-
dc.identifier.epage13670-
dc.publisher.placeUnited States-

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