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Article: MicroRNA-34a is a tumor suppressor in choriocarcinoma via regulation of Delta-like1

TitleMicroRNA-34a is a tumor suppressor in choriocarcinoma via regulation of Delta-like1
Authors
Issue Date2013
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmccancer/
Citation
Bmc Cancer, 2013, v. 13, article no. 25 How to Cite?
AbstractBackground: Choriocarcinoma is a gestational trophoblastic tumor which causes high mortality if left untreated. MicroRNAs (miRNAs) are small non protein-coding RNAs which inhibit target gene expression. The role of miRNAs in choriocarcinoma, however, is not well understood. In this study, we examined the effect of miR-34a in choriocarcinoma.Methods: MiR-34a was either inhibited or ectopically expressed transiently in two choriocarcinoma cell lines (BeWo and JEG-3) respectively. Its actions on cell invasion, proliferation and colony formation at low cell density were examined. The miR-34a putative target Notch ligand Delta-like 1 (DLL1) was identified by adoption of different approaches including: in-silico analysis, functional luciferase assay and western blotting. Real-time quantitative polymerase chain reaction was used to quantify changes in the expression of matrix proteinase in the treated cells. To nullify the effect of miR-34a ectopic expression, we activated Notch signaling through force-expression of the Notch intracellular domain in the miR-34a force-expressed cells. In addition, we studied the importance of DLL1 in BeWo cell invasion through ligand stimulation and antibody inhibition. Furthermore, the induction in tumor formation of miR-34a-inhibited BeWo cells in SCID mice was investigated.Results: Transient miR-34a force-expression significantly suppressed cell proliferation and invasion in BeWo and JEG-3 cells. In silicon miRNA target prediction, luciferase functional assays and Western blotting analysis demonstrated that miR-34a regulated DLL1 expression in both cell lines. Although force-expression of miR-34a suppressed the expression of DLL1 and NOTCH1, the extent of suppression was higher in DLL1 than NOTCH1 in both cell lines. MiR-34a-mediated DLL1 suppression led to reduced matrix metallopeptidase 9 and urokinase-type plasminogen activator expression. The effect of miR-34a on cell invasion was partially nullified by Notch signaling activation. DLL1 ligand stimulated while anti-DLL1 antibody treatment suppressed cell invasion. Mice inoculated with BeWo cells transfected with miR-34a inhibitor had significantly larger xenografts and stronger DLL1 expression than those with cells transfected with the control inhibitor.Conclusions: MiR-34a reduced cell proliferation and invasiveness, at least, partially through its inhibitory effect on DLL1. © 2013 Pang et al.; licensee BioMed Central Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/184296
ISSN
2015 Impact Factor: 3.265
2015 SCImago Journal Rankings: 1.627
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorPang, RTKen_US
dc.contributor.authorLeung, CONen_US
dc.contributor.authorLee, CLen_US
dc.contributor.authorLam, KKWen_US
dc.contributor.authorYe, TMen_US
dc.contributor.authorChiu, PCNen_US
dc.contributor.authorYeung, WSBen_US
dc.date.accessioned2013-07-04T06:11:00Z-
dc.date.available2013-07-04T06:11:00Z-
dc.date.issued2013en_US
dc.identifier.citationBmc Cancer, 2013, v. 13, article no. 25en_US
dc.identifier.issn1471-2407en_US
dc.identifier.urihttp://hdl.handle.net/10722/184296-
dc.description.abstractBackground: Choriocarcinoma is a gestational trophoblastic tumor which causes high mortality if left untreated. MicroRNAs (miRNAs) are small non protein-coding RNAs which inhibit target gene expression. The role of miRNAs in choriocarcinoma, however, is not well understood. In this study, we examined the effect of miR-34a in choriocarcinoma.Methods: MiR-34a was either inhibited or ectopically expressed transiently in two choriocarcinoma cell lines (BeWo and JEG-3) respectively. Its actions on cell invasion, proliferation and colony formation at low cell density were examined. The miR-34a putative target Notch ligand Delta-like 1 (DLL1) was identified by adoption of different approaches including: in-silico analysis, functional luciferase assay and western blotting. Real-time quantitative polymerase chain reaction was used to quantify changes in the expression of matrix proteinase in the treated cells. To nullify the effect of miR-34a ectopic expression, we activated Notch signaling through force-expression of the Notch intracellular domain in the miR-34a force-expressed cells. In addition, we studied the importance of DLL1 in BeWo cell invasion through ligand stimulation and antibody inhibition. Furthermore, the induction in tumor formation of miR-34a-inhibited BeWo cells in SCID mice was investigated.Results: Transient miR-34a force-expression significantly suppressed cell proliferation and invasion in BeWo and JEG-3 cells. In silicon miRNA target prediction, luciferase functional assays and Western blotting analysis demonstrated that miR-34a regulated DLL1 expression in both cell lines. Although force-expression of miR-34a suppressed the expression of DLL1 and NOTCH1, the extent of suppression was higher in DLL1 than NOTCH1 in both cell lines. MiR-34a-mediated DLL1 suppression led to reduced matrix metallopeptidase 9 and urokinase-type plasminogen activator expression. The effect of miR-34a on cell invasion was partially nullified by Notch signaling activation. DLL1 ligand stimulated while anti-DLL1 antibody treatment suppressed cell invasion. Mice inoculated with BeWo cells transfected with miR-34a inhibitor had significantly larger xenografts and stronger DLL1 expression than those with cells transfected with the control inhibitor.Conclusions: MiR-34a reduced cell proliferation and invasiveness, at least, partially through its inhibitory effect on DLL1. © 2013 Pang et al.; licensee BioMed Central Ltd.en_US
dc.languageengen_US
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmccancer/en_US
dc.relation.ispartofBMC Canceren_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshAnimalsen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCell Movementen_US
dc.subject.meshCell Proliferationen_US
dc.subject.meshChoriocarcinoma - Genetics - Metabolism - Pathologyen_US
dc.subject.meshComputer Simulationen_US
dc.subject.meshFemaleen_US
dc.subject.meshGene Expression Regulation, Neoplasticen_US
dc.subject.meshGene Knockdown Techniquesen_US
dc.subject.meshGenes, Reporteren_US
dc.subject.meshGenes, Tumor Suppressoren_US
dc.subject.meshHumansen_US
dc.subject.meshIntercellular Signaling Peptides And Proteins - Genetics - Metabolismen_US
dc.subject.meshMatrix Metalloproteinase 9 - Metabolismen_US
dc.subject.meshMembrane Proteins - Genetics - Metabolismen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Sciden_US
dc.subject.meshMicrornas - Genetics - Metabolismen_US
dc.subject.meshModels, Biologicalen_US
dc.subject.meshNeoplasm Invasivenessen_US
dc.subject.meshPregnancyen_US
dc.subject.meshReal-Time Polymerase Chain Reactionen_US
dc.subject.meshSignal Transductionen_US
dc.subject.meshTime Factorsen_US
dc.subject.meshTransfectionen_US
dc.subject.meshTumor Burdenen_US
dc.subject.meshUrokinase-Type Plasminogen Activator - Metabolismen_US
dc.subject.meshUterine Neoplasms - Genetics - Metabolism - Pathologyen_US
dc.titleMicroRNA-34a is a tumor suppressor in choriocarcinoma via regulation of Delta-like1en_US
dc.typeArticleen_US
dc.identifier.emailPang, RTK: rtkpang@hku.hken_US
dc.identifier.authorityPang, RTK=rp01761en_US
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/1471-2407-13-25en_US
dc.identifier.pmid23327670-
dc.identifier.scopuseid_2-s2.0-84872341676en_US
dc.identifier.hkuros222396-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84872341676&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume13en_US
dc.identifier.spagearticle no. 25-
dc.identifier.epagearticle no. 25-
dc.identifier.isiWOS:000314344500001-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridPang, RTK=7004376636en_US
dc.identifier.scopusauthoridLeung, CON=36140510700en_US
dc.identifier.scopusauthoridLee, CL=55548905900en_US
dc.identifier.scopusauthoridLam, KKW=55549676400en_US
dc.identifier.scopusauthoridYe, TM=36166071700en_US
dc.identifier.scopusauthoridChiu, PCN=55555511800en_US
dc.identifier.scopusauthoridYeung, WSB=55763794782en_US

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