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Article: The MicroRNA miR-139 suppresses metastasis and progression of hepatocellular carcinoma by down-regulating rho-kinase 2

TitleThe MicroRNA miR-139 suppresses metastasis and progression of hepatocellular carcinoma by down-regulating rho-kinase 2
Authors
KeywordsCancer Biomarker
Liver Cancer
Non-Coding RNA
Tumor Progression
Issue Date2011
PublisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/gastro
Citation
Gastroenterology, 2011, v. 140 n. 1, p. 322-331 How to Cite?
AbstractBackground & Aims: We investigated mechanisms of hepatocellular carcinoma (HCC) metastasis and identified an antimetastatic microRNA (miRNA), miR-139, that is down-regulated in human HCC samples. Methods: Effects of stable and transient expression of miRNA-139 and its inhibitors were studied in the human HCC cell lines SMMC-7721 and BEL7402; cells were analyzed for migration and invasion. Liver samples from patients with metastatic HCC were analyzed for levels of miRNA-139; data were compared with survival data using the KaplanMeier method and compared between groups by the log-rank test. Tumor formation and metastasis from human HCC MHCC97L cells that did or did not express miR-139 were analyzed in mice. Results: Down-regulation of miR-139 in HCC was associated significantly with poor prognosis of patients and features of metastatic tumors, including venous invasion, microsatellite formation, absence of tumor encapsulation, and reduced differentiation. miR-139 expression was reduced in metastatic HCC tumors compared with primary tumors. Overexpression of miR-139 in HCC cells significantly reduced cell migration and invasion in vitro and the incidence and severity of lung metastasis from orthotopic liver tumors in mice. miR-139 interacted with the 3' untranslated region of Rho-kinase 2 (ROCK2) and reduced its expression in HCC cells. Levels of miR-139 were correlated inversely with ROCK2 protein in human HCC samples. Overexpression of miR-139 did not inhibit HCC cell motility when ROCK2 was knocked down. Conclusions: The microRNA miR-139 interacts with ROCK2 and reduces its expression in HCC cells. Down-regulation of miR-139 increased the invasive abilities of HCC cells in vitro and HCC metastasis in vivo. Expression of miR-139 is reduced in human metastatic HCC samples and correlates with prognosis. © 2011 AGA Institute.
Persistent Identifierhttp://hdl.handle.net/10722/142519
ISSN
2015 Impact Factor: 18.187
2015 SCImago Journal Rankings: 7.170
ISI Accession Number ID
Funding AgencyGrant Number
Pfizer, Inc.
Hong Kong Research Grants CouncilHKU 1/06C and HKU 7/CRG/09
Funding Information:

The authors disclose the following: Irene Oi-Lin Ng has received a Research Collaborative Grant from Pfizer, Inc. The remaining authors disclose no conflicts.

References

 

DC FieldValueLanguage
dc.contributor.authorWong, CCen_HK
dc.contributor.authorWong, Cen_HK
dc.contributor.authorTung, EKen_HK
dc.contributor.authorAu, SLen_HK
dc.contributor.authorLee, JMen_HK
dc.contributor.authorPoon, RTen_HK
dc.contributor.authorMan, Ken_HK
dc.contributor.authorNg, IOen_HK
dc.date.accessioned2011-10-28T02:50:21Z-
dc.date.available2011-10-28T02:50:21Z-
dc.date.issued2011en_HK
dc.identifier.citationGastroenterology, 2011, v. 140 n. 1, p. 322-331en_HK
dc.identifier.issn0016-5085en_HK
dc.identifier.urihttp://hdl.handle.net/10722/142519-
dc.description.abstractBackground & Aims: We investigated mechanisms of hepatocellular carcinoma (HCC) metastasis and identified an antimetastatic microRNA (miRNA), miR-139, that is down-regulated in human HCC samples. Methods: Effects of stable and transient expression of miRNA-139 and its inhibitors were studied in the human HCC cell lines SMMC-7721 and BEL7402; cells were analyzed for migration and invasion. Liver samples from patients with metastatic HCC were analyzed for levels of miRNA-139; data were compared with survival data using the KaplanMeier method and compared between groups by the log-rank test. Tumor formation and metastasis from human HCC MHCC97L cells that did or did not express miR-139 were analyzed in mice. Results: Down-regulation of miR-139 in HCC was associated significantly with poor prognosis of patients and features of metastatic tumors, including venous invasion, microsatellite formation, absence of tumor encapsulation, and reduced differentiation. miR-139 expression was reduced in metastatic HCC tumors compared with primary tumors. Overexpression of miR-139 in HCC cells significantly reduced cell migration and invasion in vitro and the incidence and severity of lung metastasis from orthotopic liver tumors in mice. miR-139 interacted with the 3' untranslated region of Rho-kinase 2 (ROCK2) and reduced its expression in HCC cells. Levels of miR-139 were correlated inversely with ROCK2 protein in human HCC samples. Overexpression of miR-139 did not inhibit HCC cell motility when ROCK2 was knocked down. Conclusions: The microRNA miR-139 interacts with ROCK2 and reduces its expression in HCC cells. Down-regulation of miR-139 increased the invasive abilities of HCC cells in vitro and HCC metastasis in vivo. Expression of miR-139 is reduced in human metastatic HCC samples and correlates with prognosis. © 2011 AGA Institute.en_HK
dc.languageengen_US
dc.publisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/gastroen_HK
dc.relation.ispartofGastroenterologyen_HK
dc.subjectCancer Biomarkeren_HK
dc.subjectLiver Canceren_HK
dc.subjectNon-Coding RNAen_HK
dc.subjectTumor Progressionen_HK
dc.subject.meshCarcinoma, Hepatocellular - metabolism - mortality - secondary-
dc.subject.meshCell Line, Tumor-
dc.subject.meshLiver Neoplasms - metabolism - mortality - pathology-
dc.subject.meshMicroRNAs - metabolism-
dc.subject.meshrho-Associated Kinases - analysis - metabolism-
dc.titleThe MicroRNA miR-139 suppresses metastasis and progression of hepatocellular carcinoma by down-regulating rho-kinase 2en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0016-5085&volume=140&issue=1&spage=322&epage=331&date=2011&atitle=The+microRNA+miR-139+suppresses+metastasis+and+progression+of+hepatocellular+carcinoma+by+down-regulating+Rho-kinase+2-
dc.identifier.emailWong, CC: carmencl@pathology.hku.hken_HK
dc.identifier.emailWong, C: jackwong@pathology.hku.hken_HK
dc.identifier.emailPoon, RT: poontp@hkucc.hku.hken_HK
dc.identifier.emailMan, K: kwanman@hkucc.hku.hken_HK
dc.identifier.emailNg, IO: iolng@hkucc.hku.hken_HK
dc.identifier.authorityWong, CC=rp01602en_HK
dc.identifier.authorityWong, C=rp00231en_HK
dc.identifier.authorityPoon, RT=rp00446en_HK
dc.identifier.authorityMan, K=rp00417en_HK
dc.identifier.authorityNg, IO=rp00335en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1053/j.gastro.2010.10.006en_HK
dc.identifier.pmid20951699-
dc.identifier.scopuseid_2-s2.0-78650436438en_HK
dc.identifier.hkuros184058en_US
dc.identifier.hkuros205571-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78650436438&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume140en_HK
dc.identifier.issue1en_HK
dc.identifier.spage322en_HK
dc.identifier.epage331en_HK
dc.identifier.eissn1528-0012-
dc.identifier.isiWOS:000285503200047-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f10007732956-
dc.identifier.scopusauthoridWong, CC=24823630000en_HK
dc.identifier.scopusauthoridWong, C=16314668400en_HK
dc.identifier.scopusauthoridTung, EK=37032220600en_HK
dc.identifier.scopusauthoridAu, SL=37030494200en_HK
dc.identifier.scopusauthoridLee, JM=37031441700en_HK
dc.identifier.scopusauthoridPoon, RT=7103097223en_HK
dc.identifier.scopusauthoridMan, K=7101754072en_HK
dc.identifier.scopusauthoridNg, IO=7102753722en_HK

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