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Article: MicroRNA-616 induces androgen-independent growth of prostate cancer cells by suppressing expression of tissue factor pathway inhibitor TFPI-2

TitleMicroRNA-616 induces androgen-independent growth of prostate cancer cells by suppressing expression of tissue factor pathway inhibitor TFPI-2
Authors
KeywordsMedical sciences
Oncology
Issue Date2011
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2011, v. 71 n. 2, p. 583-592 How to Cite?
AbstractExpression of microRNA genes is profoundly altered in cancer but their role in the development of androgenindependent prostate cancer has received limited attention as yet. In this study, we report a functional impact in prostate cancer cells for overexpression of the microRNA miR-616, which occurred consistently in cells that were androgen-independent (AI) versus androgen-dependent (AD). miR-616 overexpression was confirmed in malignant prostate tissues as opposed to benign prostate specimens. Stable miR-616 overexpression in LNCaP cells by a lentiviral-based approach stimulated AI prostate cancer cell proliferation in vitro whereas concomitantly reducing androgen-induced cell growth. More importantly, miR-616 overexpressing LNCaP cells overcame castration resistance as shown by an enhanced ability to proliferate in vivo after bilateral orchiectomy. Conversely, antagonizing miR-616 in AI prostate cancer cells yielded opposite effects. Microarray profiling and bioinformatics analysis identified the tissue factor pathway inhibitor TFPI-2 mRNA as a candidate downstream target of miR-616. In support of this candidacy, we documented interactions between miR-616 and the 30UTR of TFPI-2 and determined TFPI-2 expression to be inversely correlated to miR-616 in a series of prostate cell lines and clinical specimens. Notably, reexpression of TFPI-2 in LNCaP cells with stable miR-616 overexpression rescued the AD phenotype, as shown by a restoration of androgen dependence and cell growth inhibition. Taken together, our findings define a functional involvement for miR-616 and TFPI-2 in the development and maintenance of androgen-independent prostate cancer. © 2011 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/126692
ISSN
2014 Impact Factor: 9.329
2013 SCImago Journal Rankings: 5.627
ISI Accession Number ID
Funding AgencyGrant Number
University of Hong Kong
Funding Information:

This work was generously supported by The University of Hong Kong Small Project Funding Program.

References

 

DC FieldValueLanguage
dc.contributor.authorMa, Sen_HK
dc.contributor.authorChan, YPen_HK
dc.contributor.authorKwan, PSen_HK
dc.contributor.authorLee, TKen_HK
dc.contributor.authorYan, Men_HK
dc.contributor.authorTang, KHen_HK
dc.contributor.authorLing, MTen_HK
dc.contributor.authorVielkind, JRen_HK
dc.contributor.authorGuan, XYen_HK
dc.contributor.authorChan, KWen_HK
dc.date.accessioned2010-10-31T12:43:01Z-
dc.date.available2010-10-31T12:43:01Z-
dc.date.issued2011en_HK
dc.identifier.citationCancer Research, 2011, v. 71 n. 2, p. 583-592en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/126692-
dc.description.abstractExpression of microRNA genes is profoundly altered in cancer but their role in the development of androgenindependent prostate cancer has received limited attention as yet. In this study, we report a functional impact in prostate cancer cells for overexpression of the microRNA miR-616, which occurred consistently in cells that were androgen-independent (AI) versus androgen-dependent (AD). miR-616 overexpression was confirmed in malignant prostate tissues as opposed to benign prostate specimens. Stable miR-616 overexpression in LNCaP cells by a lentiviral-based approach stimulated AI prostate cancer cell proliferation in vitro whereas concomitantly reducing androgen-induced cell growth. More importantly, miR-616 overexpressing LNCaP cells overcame castration resistance as shown by an enhanced ability to proliferate in vivo after bilateral orchiectomy. Conversely, antagonizing miR-616 in AI prostate cancer cells yielded opposite effects. Microarray profiling and bioinformatics analysis identified the tissue factor pathway inhibitor TFPI-2 mRNA as a candidate downstream target of miR-616. In support of this candidacy, we documented interactions between miR-616 and the 30UTR of TFPI-2 and determined TFPI-2 expression to be inversely correlated to miR-616 in a series of prostate cell lines and clinical specimens. Notably, reexpression of TFPI-2 in LNCaP cells with stable miR-616 overexpression rescued the AD phenotype, as shown by a restoration of androgen dependence and cell growth inhibition. Taken together, our findings define a functional involvement for miR-616 and TFPI-2 in the development and maintenance of androgen-independent prostate cancer. © 2011 American Association for Cancer Research.en_HK
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_HK
dc.relation.ispartofCancer Researchen_HK
dc.subjectMedical sciences-
dc.subjectOncology-
dc.titleMicroRNA-616 induces androgen-independent growth of prostate cancer cells by suppressing expression of tissue factor pathway inhibitor TFPI-2en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-5472&volume=71&issue=2&spage=583&epage=592&date=2011&atitle=MicroRNA-616+induces+androgen-independent+growth+of+prostate+cancer+cells+by+suppressing+expression+of+Tissue+Factor+Pathway+Inhibitor+TFPI-2-
dc.identifier.emailMa, S:sma@pathology.hku.hken_HK
dc.identifier.emailLee, TK:tkwlee@hkucc.hku.hken_HK
dc.identifier.emailLing, MT:patling@hkucc.hku.hken_HK
dc.identifier.emailGuan, XY:xyguan@hkucc.hku.hken_HK
dc.identifier.emailChan, KW:hrmtckw@hku.hken_HK
dc.identifier.authorityMa, S=rp00506en_HK
dc.identifier.authorityLee, TK=rp00447en_HK
dc.identifier.authorityLing, MT=rp00449en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.identifier.authorityChan, KW=rp00330en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/0008-5472.CAN-10-2587en_HK
dc.identifier.pmid21224345-
dc.identifier.scopuseid_2-s2.0-78751527881en_HK
dc.identifier.hkuros171391en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78751527881&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume71en_HK
dc.identifier.issue2en_HK
dc.identifier.spage583en_HK
dc.identifier.epage592en_HK
dc.identifier.eissn1538-7445-
dc.identifier.isiWOS:000286193900029-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridMa, S=16444895800en_HK
dc.identifier.scopusauthoridChan, YP=14009821700en_HK
dc.identifier.scopusauthoridKwan, PS=36698058700en_HK
dc.identifier.scopusauthoridLee, TK=7501439435en_HK
dc.identifier.scopusauthoridYan, M=16030155400en_HK
dc.identifier.scopusauthoridTang, KH=24781597200en_HK
dc.identifier.scopusauthoridLing, MT=7102229780en_HK
dc.identifier.scopusauthoridVielkind, JR=7004097540en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK
dc.identifier.scopusauthoridChan, KW=16444133100en_HK

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