Links for fulltext
     (May Require Subscription)
Supplementary

Article: Suppression of tumorigenesis and metastasis of hepatocellular carcinoma by shRNA interference targeting on homeoprotein Six1

TitleSuppression of tumorigenesis and metastasis of hepatocellular carcinoma by shRNA interference targeting on homeoprotein Six1
Authors
KeywordscDNA microarray
Hepatocellular carcinoma
Homeoprotein Six1
Interference
Metastasis
Short hairpin RNA (shRNA)
Issue Date2010
PublisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
Citation
International Journal Of Cancer, 2010, v. 127 n. 4, p. 859-872 How to Cite?
AbstractWe previously demonstrated that the overexpression of homeoprotein Six1 in hepatocellular carcinoma (HCC) patients is associated with venous infiltration, advanced pathologic tumor metastasis (pTNM) stage and poor overall survival rate (Ng et al. Br J Cancer 2006;95:1050-5). In this study, short hairpin RNA (shRNA) interference approach was used to suppress the expression of Six1 in a metastatic HCC cell line MHCC97L. Stable transfectant MHCC97L-shSix1 carrying Six1-specific shRNA plasmid was established to downregulate Six1 expression to about 40% when compared with MHCC97L-Control. In vitro functional assays demonstrated that the growth rate and proliferation ability of MHCC97L-shSix1 cells were markedly decreased. Moreover, significant decrease of cell motility and invasiveness were observed in MHCC97L-shSix1 cells. Data from in vivo xenograft tumorigenesis model demonstrated that the size of tumor in MHCC97L-shSix1 group was dramatically reduced. Experimental and spontaneous metastasis models indicated that targeting Six1 suppression noticeably reduced the pulmonary metastasis in MHCC97L-shSix1 group. To identify Six1-regulated targets, cDNA microarray was employed to compare the expression profiles of MHCC97L-Control and MHCC97L-shSix1 cells. Twenty-eight downregulated and 24 upregulated genes with known functions were identified in MHCC97L-shSix1. The functions of these target genes are involved in diverse biological activities. Our data suggest that Six1 may be involved in regulation of proliferation and invasiveness of HCC; thus targeting suppression of Six1 is a viable option for treating HCC patients. © 2009 UICC.
Persistent Identifierhttp://hdl.handle.net/10722/123820
ISSN
2015 Impact Factor: 5.531
2015 SCImago Journal Rankings: 2.657
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorNg, KTPen_HK
dc.contributor.authorLee, TKWen_HK
dc.contributor.authorCheng, Qen_HK
dc.contributor.authorWo, JYHen_HK
dc.contributor.authorSun, CKWen_HK
dc.contributor.authorGuo, DYen_HK
dc.contributor.authorLim, ZXen_HK
dc.contributor.authorLo, CMen_HK
dc.contributor.authorPoon, RTPen_HK
dc.contributor.authorFan, STen_HK
dc.contributor.authorMan, Ken_HK
dc.date.accessioned2010-09-28T04:32:09Z-
dc.date.available2010-09-28T04:32:09Z-
dc.date.issued2010en_HK
dc.identifier.citationInternational Journal Of Cancer, 2010, v. 127 n. 4, p. 859-872en_HK
dc.identifier.issn0020-7136en_HK
dc.identifier.urihttp://hdl.handle.net/10722/123820-
dc.description.abstractWe previously demonstrated that the overexpression of homeoprotein Six1 in hepatocellular carcinoma (HCC) patients is associated with venous infiltration, advanced pathologic tumor metastasis (pTNM) stage and poor overall survival rate (Ng et al. Br J Cancer 2006;95:1050-5). In this study, short hairpin RNA (shRNA) interference approach was used to suppress the expression of Six1 in a metastatic HCC cell line MHCC97L. Stable transfectant MHCC97L-shSix1 carrying Six1-specific shRNA plasmid was established to downregulate Six1 expression to about 40% when compared with MHCC97L-Control. In vitro functional assays demonstrated that the growth rate and proliferation ability of MHCC97L-shSix1 cells were markedly decreased. Moreover, significant decrease of cell motility and invasiveness were observed in MHCC97L-shSix1 cells. Data from in vivo xenograft tumorigenesis model demonstrated that the size of tumor in MHCC97L-shSix1 group was dramatically reduced. Experimental and spontaneous metastasis models indicated that targeting Six1 suppression noticeably reduced the pulmonary metastasis in MHCC97L-shSix1 group. To identify Six1-regulated targets, cDNA microarray was employed to compare the expression profiles of MHCC97L-Control and MHCC97L-shSix1 cells. Twenty-eight downregulated and 24 upregulated genes with known functions were identified in MHCC97L-shSix1. The functions of these target genes are involved in diverse biological activities. Our data suggest that Six1 may be involved in regulation of proliferation and invasiveness of HCC; thus targeting suppression of Six1 is a viable option for treating HCC patients. © 2009 UICC.en_HK
dc.languageeng-
dc.publisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/homeen_HK
dc.relation.ispartofInternational Journal of Canceren_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectcDNA microarrayen_HK
dc.subjectHepatocellular carcinomaen_HK
dc.subjectHomeoprotein Six1en_HK
dc.subjectInterferenceen_HK
dc.subjectMetastasisen_HK
dc.subjectShort hairpin RNA (shRNA)en_HK
dc.subject.meshCarcinoma, Hepatocellular - genetics - prevention and control - secondary-
dc.subject.meshHomeodomain Proteins - antagonists and inhibitors - genetics - metabolism-
dc.subject.meshKidney Neoplasms - genetics - prevention and control - secondary-
dc.subject.meshLiver Neoplasms, Experimental - genetics - pathology - prevention and control-
dc.subject.meshRNA, Small Interfering - pharmacology-
dc.titleSuppression of tumorigenesis and metastasis of hepatocellular carcinoma by shRNA interference targeting on homeoprotein Six1en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0020-7136&volume=127&issue=4&spage=859&epage=872&date=2010&atitle=Suppression+of+tumorigenesis+and+metastasis+of+hepatocellular+carcinoma+by+shRNA+interference+targeting+on+homeoprotein+Six1-
dc.identifier.emailNg, KTP: ledodes@hku.hken_HK
dc.identifier.emailLee, TKW: tkwlee@hkucc.hku.hken_HK
dc.identifier.emailLo, CM: chungmlo@hkucc.hku.hken_HK
dc.identifier.emailPoon, RTP: poontp@hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.emailMan, K: kwanman@hku.hken_HK
dc.identifier.authorityNg, KTP=rp01720en_HK
dc.identifier.authorityLee, TKW=rp00447en_HK
dc.identifier.authorityLo, CM=rp00412en_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.identifier.authorityMan, K=rp00417en_HK
dc.description.naturepostprint-
dc.identifier.doi10.1002/ijc.25105en_HK
dc.identifier.pmid20013809-
dc.identifier.scopuseid_2-s2.0-77954709872en_HK
dc.identifier.hkuros183222-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77954709872&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume127en_HK
dc.identifier.issue4en_HK
dc.identifier.spage859en_HK
dc.identifier.epage872en_HK
dc.identifier.isiWOS:000279971500013-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridNg, KTP=7403178513en_HK
dc.identifier.scopusauthoridLee, TKW=7501439435en_HK
dc.identifier.scopusauthoridCheng, Q=16024087700en_HK
dc.identifier.scopusauthoridWo, JYH=7003466728en_HK
dc.identifier.scopusauthoridSun, CKW=7404248685en_HK
dc.identifier.scopusauthoridGuo, DY=36171425600en_HK
dc.identifier.scopusauthoridLim, ZX=25822628500en_HK
dc.identifier.scopusauthoridLo, CM=7401771672en_HK
dc.identifier.scopusauthoridPoon, RTP=7103097223en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK
dc.identifier.scopusauthoridMan, K=7101754072en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats