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Article: MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells

TitleMicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells
Authors
Issue Date2010
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
Citation
Carcinogenesis, 2010, v. 31 n. 6, p. 1037-1044 How to Cite?
AbstractMicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of other genes by transcriptional inhibition or translational repression. miR-34a is a known tumor suppressor gene and inhibits abnormal cell growth. However, its role in other tumorigenic processes is not fully known. This study aimed to investigate the action of miR-34a on cell invasion. We found that miR-34a is expressed at various levels in cervical cancer (HeLa, SiHa, C4I, C33a and CaSki) and trophoblast (BeWo and JAR) cell lines. Transient forced expression of miR-34a did not affect the proliferation of these cell lines. Computational miRNA target prediction suggested that Notch1 and Jagged1 were targets of miR-34a. By using functional assays, miR-34a was demonstrated to bind to the 3# untranslated regions of Notch1 and Jagged1. Forced expression of miR-34a altered the expression of Notch1 and Jagged1 protein as well as Notch signaling as shown by the response of Hairy Enhancer of Split-1 protein to these treatments using western blot analysis. Forced expression of miR-34a suppressed the invasiveness of HeLa and JAR cells. By using γ-secretase inhibitor (N-[N-(3,5-difluorophenacetyl)l-alanyl]-S-phenylglycine t-butyl ester) that interfered Notch signaling and RNA interference that knockdown Notch1 expression, we confirmed that downregulation of Notch1 reduced the invasiveness of the cells. Transfection of intracellular domain of Notch nullifies the effect of miR-34a on the invasiveness of the cells. Besides, we identified that miR-34a affected cell invasion by regulating expression of urokinase plasminogen activator through Notch. Our results provide evidence that miR-34a inhibits invasiveness through regulation of the Notch pathway and its downstream matrix degrading enzyme. © The Author 2010. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org.
Persistent Identifierhttp://hdl.handle.net/10722/125544
ISSN
2015 Impact Factor: 4.874
2015 SCImago Journal Rankings: 2.439
ISI Accession Number ID
Funding AgencyGrant Number
Committee on Research and Conference Grant
The University of Hong Kong
Hong Kong Research Grant CouncilHKU 780308M
Funding Information:

Committee on Research and Conference Grant, The University of Hong Kong, Hong Kong Research Grant Council (RGC grants HKU 780308M).

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorPang, RTKen_HK
dc.contributor.authorLeung, COen_HK
dc.contributor.authorYe, TMen_HK
dc.contributor.authorLiu, Wen_HK
dc.contributor.authorChiu, PCNen_HK
dc.contributor.authorLam, KKWen_HK
dc.contributor.authorLee, KFen_HK
dc.contributor.authorYeung, WSBen_HK
dc.date.accessioned2010-10-31T11:37:25Z-
dc.date.available2010-10-31T11:37:25Z-
dc.date.issued2010en_HK
dc.identifier.citationCarcinogenesis, 2010, v. 31 n. 6, p. 1037-1044en_HK
dc.identifier.issn0143-3334en_HK
dc.identifier.urihttp://hdl.handle.net/10722/125544-
dc.description.abstractMicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of other genes by transcriptional inhibition or translational repression. miR-34a is a known tumor suppressor gene and inhibits abnormal cell growth. However, its role in other tumorigenic processes is not fully known. This study aimed to investigate the action of miR-34a on cell invasion. We found that miR-34a is expressed at various levels in cervical cancer (HeLa, SiHa, C4I, C33a and CaSki) and trophoblast (BeWo and JAR) cell lines. Transient forced expression of miR-34a did not affect the proliferation of these cell lines. Computational miRNA target prediction suggested that Notch1 and Jagged1 were targets of miR-34a. By using functional assays, miR-34a was demonstrated to bind to the 3# untranslated regions of Notch1 and Jagged1. Forced expression of miR-34a altered the expression of Notch1 and Jagged1 protein as well as Notch signaling as shown by the response of Hairy Enhancer of Split-1 protein to these treatments using western blot analysis. Forced expression of miR-34a suppressed the invasiveness of HeLa and JAR cells. By using γ-secretase inhibitor (N-[N-(3,5-difluorophenacetyl)l-alanyl]-S-phenylglycine t-butyl ester) that interfered Notch signaling and RNA interference that knockdown Notch1 expression, we confirmed that downregulation of Notch1 reduced the invasiveness of the cells. Transfection of intracellular domain of Notch nullifies the effect of miR-34a on the invasiveness of the cells. Besides, we identified that miR-34a affected cell invasion by regulating expression of urokinase plasminogen activator through Notch. Our results provide evidence that miR-34a inhibits invasiveness through regulation of the Notch pathway and its downstream matrix degrading enzyme. © The Author 2010. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/en_HK
dc.relation.ispartofCarcinogenesisen_HK
dc.rightsPre-print: Journal Title] ©: [year] [owner as specified on the article] Published by Oxford University Press [on behalf of xxxxxx]. All rights reserved. Pre-print (Once an article is published, preprint notice should be amended to): This is an electronic version of an article published in [include the complete citation information for the final version of the Article as published in the print edition of the Journal.] Post-print: This is a pre-copy-editing, author-produced PDF of an article accepted for publication in [insert journal title] following peer review. The definitive publisher-authenticated version [insert complete citation information here] is available online at: xxxxxxx [insert URL that the author will receive upon publication here].-
dc.subject.meshCalcium-Binding Proteins - genetics-
dc.subject.meshChoriocarcinoma - genetics - pathology-
dc.subject.meshDown-Regulation-
dc.subject.meshIntercellular Signaling Peptides and Proteins - genetics-
dc.subject.meshMembrane Proteins - genetics-
dc.titleMicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0143-3334&volume=31&issue=6&spage=1037&epage=1044&date=2010&atitle=MicroRNA-34a+suppresses+invasion+through+downregulation+of+Notch1+and+Jagged1+in+cervical+carcinoma+and+choriocarcinoma+cellsen_HK
dc.identifier.emailPang, RTK: rtkpang@hku.hken_HK
dc.identifier.emailChiu, PCN: pchiucn@hku.hken_HK
dc.identifier.emailLee, KF: ckflee@hku.hken_HK
dc.identifier.authorityPang, RTK=rp01761en_HK
dc.identifier.authorityChiu, PCN=rp00424en_HK
dc.identifier.authorityLee, KF=rp00458en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1093/carcin/bgq066en_HK
dc.identifier.pmid20351093-
dc.identifier.scopuseid_2-s2.0-77953920780en_HK
dc.identifier.hkuros180810en_HK
dc.identifier.hkuros176925-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77953920780&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume31en_HK
dc.identifier.issue6en_HK
dc.identifier.spage1037en_HK
dc.identifier.epage1044en_HK
dc.identifier.eissn1460-2180-
dc.identifier.isiWOS:000278218500011-
dc.publisher.placeUnited Kingdomen_HK
dc.relation.projectA study on glycodelin-A induced differentiation of trophoblast cells-
dc.identifier.scopusauthoridPang, RTK=7004376636en_HK
dc.identifier.scopusauthoridLeung, CO=36140510700en_HK
dc.identifier.scopusauthoridYe, TM=36166071700en_HK
dc.identifier.scopusauthoridLiu, W=35548548500en_HK
dc.identifier.scopusauthoridChiu, PCN=25959969200en_HK
dc.identifier.scopusauthoridLam, KKW=25637362300en_HK
dc.identifier.scopusauthoridLee, KF=26643097500en_HK
dc.identifier.scopusauthoridYeung, WSB=55763794874en_HK

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