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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
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TitleMicroRNA-616 induces androgen-independent growth of prostate cancer cells by suppressing expression of tissue factor pathway inhibitor TFPI-2
 
AuthorsMa, S2 1
Chan, YP2
Kwan, PS2
Lee, TK2
Yan, M3
Tang, KH2
Ling, MT6
Vielkind, JR5 4
Guan, XY2
Chan, KW2
 
KeywordsMedical sciences
Oncology
 
Issue Date2011
 
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
 
CitationCancer Research, 2011, v. 71 n. 2, p. 583-592 [How to Cite?]
DOI: http://dx.doi.org/10.1158/0008-5472.CAN-10-2587
 
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.
 
ISSN0008-5472
2013 Impact Factor: 9.284
2013 SCImago Journal Rankings: 5.627
 
DOIhttp://dx.doi.org/10.1158/0008-5472.CAN-10-2587
 
ISI Accession Number IDWOS:000286193900029
Funding AgencyGrant Number
University of Hong Kong
Funding Information:

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

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorMa, S
 
dc.contributor.authorChan, YP
 
dc.contributor.authorKwan, PS
 
dc.contributor.authorLee, TK
 
dc.contributor.authorYan, M
 
dc.contributor.authorTang, KH
 
dc.contributor.authorLing, MT
 
dc.contributor.authorVielkind, JR
 
dc.contributor.authorGuan, XY
 
dc.contributor.authorChan, KW
 
dc.date.accessioned2010-10-31T12:43:01Z
 
dc.date.available2010-10-31T12:43:01Z
 
dc.date.issued2011
 
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.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationCancer Research, 2011, v. 71 n. 2, p. 583-592 [How to Cite?]
DOI: http://dx.doi.org/10.1158/0008-5472.CAN-10-2587
 
dc.identifier.doihttp://dx.doi.org/10.1158/0008-5472.CAN-10-2587
 
dc.identifier.eissn1538-7445
 
dc.identifier.epage592
 
dc.identifier.hkuros171391
 
dc.identifier.isiWOS:000286193900029
Funding AgencyGrant Number
University of Hong Kong
Funding Information:

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

 
dc.identifier.issn0008-5472
2013 Impact Factor: 9.284
2013 SCImago Journal Rankings: 5.627
 
dc.identifier.issue2
 
dc.identifier.openurl
 
dc.identifier.pmid21224345
 
dc.identifier.scopuseid_2-s2.0-78751527881
 
dc.identifier.spage583
 
dc.identifier.urihttp://hdl.handle.net/10722/126692
 
dc.identifier.volume71
 
dc.languageeng
 
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofCancer Research
 
dc.relation.referencesReferences in Scopus
 
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-2
 
dc.typeArticle
 
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<description.abstract>Expression 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. &#169; 2011 American Association for Cancer Research.</description.abstract>
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Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. The University of Hong Kong
  3. Shanghai Jiaotong University
  4. BC Cancer Research Centre
  5. The University of British Columbia
  6. Queensland University of Technology