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Article: Identification of small molecules that suppress microRNA function and reverse tumorigenesis

TitleIdentification of small molecules that suppress microRNA function and reverse tumorigenesis
Authors
Issue Date2010
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 2010, v. 285 n. 32, p. 24707-24716 How to Cite?
AbstractMicroRNAs (miRNAs) act in post-transcriptional gene silencing and are proposed to function in a wide spectrum of pathologies, including cancers and viral diseases. Currently, to our knowledge, no detailed mechanistic characterization of small molecules that interrupt miRNA pathways have been reported. In screening a small chemical library, we identified compounds that suppress RNA interference activity in cultured cells. Two compounds were characterized; one impaired Dicer activity while the other blocked small RNA-loading into an Argonaute 2 (AGO2) complex. We developed a cell-based model of miRNA-dependent tumorigenesis, and using this model, we observed that treatment of cells with either of the two compounds effectively neutralized tumor growth. These findings indicate that miRNA pathway-suppressing small molecules could potentially reverse tumorigenesis.
Persistent Identifierhttp://hdl.handle.net/10722/157598
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID
Funding AgencyGrant Number
National Institutes of Health1R01 GM087738-01A1
NIAID
NIH
Japan Society for the Promotion of Science
Funding Information:

This work was supported, in whole or in part, by National Institutes of Health Grant 1R01 GM087738-01A1 (to R. S. H.) and by intramural funds from NIAID, NIH and the Intramural AIDS Targeted Antiviral Program from the office of the Director, NIH (to K.-T. J.).

References

 

DC FieldValueLanguage
dc.contributor.authorWatashi, Ken_US
dc.contributor.authorYeung, MLen_US
dc.contributor.authorStarost, MFen_US
dc.contributor.authorHosmane, RSen_US
dc.contributor.authorJeang, KTen_US
dc.date.accessioned2012-08-08T08:51:35Z-
dc.date.available2012-08-08T08:51:35Z-
dc.date.issued2010en_US
dc.identifier.citationJournal Of Biological Chemistry, 2010, v. 285 n. 32, p. 24707-24716en_US
dc.identifier.issn0021-9258en_US
dc.identifier.urihttp://hdl.handle.net/10722/157598-
dc.description.abstractMicroRNAs (miRNAs) act in post-transcriptional gene silencing and are proposed to function in a wide spectrum of pathologies, including cancers and viral diseases. Currently, to our knowledge, no detailed mechanistic characterization of small molecules that interrupt miRNA pathways have been reported. In screening a small chemical library, we identified compounds that suppress RNA interference activity in cultured cells. Two compounds were characterized; one impaired Dicer activity while the other blocked small RNA-loading into an Argonaute 2 (AGO2) complex. We developed a cell-based model of miRNA-dependent tumorigenesis, and using this model, we observed that treatment of cells with either of the two compounds effectively neutralized tumor growth. These findings indicate that miRNA pathway-suppressing small molecules could potentially reverse tumorigenesis.en_US
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_US
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.subject.mesh3T3 Cellsen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCell Proliferationen_US
dc.subject.meshGene Expression Regulation, Neoplasticen_US
dc.subject.meshGene Silencingen_US
dc.subject.meshHela Cellsen_US
dc.subject.meshHumansen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Nudeen_US
dc.subject.meshMicrornas - Metabolismen_US
dc.subject.meshModels, Biologicalen_US
dc.subject.meshNeoplasm Transplantationen_US
dc.subject.meshNeoplasms - Genetics - Therapyen_US
dc.subject.meshPhenotypeen_US
dc.subject.meshRna Interferenceen_US
dc.titleIdentification of small molecules that suppress microRNA function and reverse tumorigenesisen_US
dc.typeArticleen_US
dc.identifier.emailYeung, ML:pmlyeung@hku.hken_US
dc.identifier.authorityYeung, ML=rp01402en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1074/jbc.M109.062976en_US
dc.identifier.pmid20529860-
dc.identifier.scopuseid_2-s2.0-77955287613en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77955287613&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume285en_US
dc.identifier.issue32en_US
dc.identifier.spage24707en_US
dc.identifier.epage24716en_US
dc.identifier.isiWOS:000280542100043-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridWatashi, K=6603024689en_US
dc.identifier.scopusauthoridYeung, ML=8350940900en_US
dc.identifier.scopusauthoridStarost, MF=6602999509en_US
dc.identifier.scopusauthoridHosmane, RS=7005420161en_US
dc.identifier.scopusauthoridJeang, KT=7004824803en_US

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