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Article: Two-tiered approach identifies a network of cancer and liver disease-related genes regulated by miR-122

TitleTwo-tiered approach identifies a network of cancer and liver disease-related genes regulated by miR-122
Authors
Issue Date2011
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, 2011, v. 286 n. 20, p. 18066-18078 How to Cite?
AbstractMicroRNAs function as important regulators of gene expression and are commonly linked to development, differentiation, and diseases such as cancer. To better understand their roles in various biological processes, identification of genes targeted by microRNAs is necessary. Although prediction tools have significantly helped with this task, experimental approaches are ultimately required for extensive target search and validation. We employed two independent yet complementary high throughput approaches to map a large set of mRNAs regulated by miR-122, a liver-specific microRNA implicated in regulation of fatty acid and cholesterol metabolism, hepatitis C infection, and hepatocellular carcinoma. The combination of luciferase reporterbased screening and shotgun proteomics resulted in the identification of 260 proteins significantly down-regulated in response to miR-122 in at least one method, 113 of which contain predicted miR-122 target sites. These proteins are enriched for functions associated with the cell cycle, differentiation, proliferation, and apoptosis. Among these miR-122-sensitive proteins, we identified a large group with strong connections to liver metabolism, diseases, and hepatocellular carcinoma. Additional analyses, including examination of consensus binding motifs for both miR-122 and target sequences, provide further insight into miR-122 function.
Persistent Identifierhttp://hdl.handle.net/10722/135557
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
National Institutes of HealthGM076536
GM067779
GM088624
Welch FoundationF-1515
Packard Foundation
NCI Center for Cancer Research
Children's Cancer Research Institute
University of Texas Health Science Center at San Antonio
SwitchGear Genomics
Funding Information:

This work was supported, in whole or in part, by National Institutes of Health Grants GM076536, GM067779, and GM088624, and Grant F-1515 from the Welch Foundation and by the Packard Foundation. (to E. M. M.) and the NCI Center for Cancer Research Intramural Research Program (to the B. A. S. laboratory). This work was also supported by the Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio (to the L. O. F. P. laboratory), and by SwitchGear Genomics. N. D. T., S. F. A., and P. J. C. are employees of and hold stock in SwitchGear Genomics. SwitchGear Genomics sells 3'UTR reporter vectors commercially. SwitchGear Genomics is the owner by assignment of patents or patent applications related to the 3'UTR reporter platform.

References

 

DC FieldValueLanguage
dc.contributor.authorBoutz, DRen_HK
dc.contributor.authorCollins, PJen_HK
dc.contributor.authorSuresh, Uen_HK
dc.contributor.authorLu, Men_HK
dc.contributor.authorRamírez, CMen_HK
dc.contributor.authorFernándezHernando, Cen_HK
dc.contributor.authorHuang, Yen_HK
dc.contributor.authorAbreu, RDSen_HK
dc.contributor.authorLe, SYen_HK
dc.contributor.authorShapiro, BAen_HK
dc.contributor.authorLiu, AMen_HK
dc.contributor.authorLuk, JMen_HK
dc.contributor.authorAldred, SFen_HK
dc.contributor.authorTrinklein, NDen_HK
dc.contributor.authorMarcotte, EMen_HK
dc.contributor.authorPenalva, LOFen_HK
dc.date.accessioned2011-07-27T01:37:06Z-
dc.date.available2011-07-27T01:37:06Z-
dc.date.issued2011en_HK
dc.identifier.citationJournal Of Biological Chemistry, 2011, v. 286 n. 20, p. 18066-18078en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/135557-
dc.description.abstractMicroRNAs function as important regulators of gene expression and are commonly linked to development, differentiation, and diseases such as cancer. To better understand their roles in various biological processes, identification of genes targeted by microRNAs is necessary. Although prediction tools have significantly helped with this task, experimental approaches are ultimately required for extensive target search and validation. We employed two independent yet complementary high throughput approaches to map a large set of mRNAs regulated by miR-122, a liver-specific microRNA implicated in regulation of fatty acid and cholesterol metabolism, hepatitis C infection, and hepatocellular carcinoma. The combination of luciferase reporterbased screening and shotgun proteomics resulted in the identification of 260 proteins significantly down-regulated in response to miR-122 in at least one method, 113 of which contain predicted miR-122 target sites. These proteins are enriched for functions associated with the cell cycle, differentiation, proliferation, and apoptosis. Among these miR-122-sensitive proteins, we identified a large group with strong connections to liver metabolism, diseases, and hepatocellular carcinoma. Additional analyses, including examination of consensus binding motifs for both miR-122 and target sequences, provide further insight into miR-122 function.en_HK
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_HK
dc.relation.ispartofJournal of Biological Chemistryen_HK
dc.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.-
dc.subject.meshCarcinoma, Hepatocellular - genetics - metabolism-
dc.subject.meshGenes, Neoplasm-
dc.subject.meshLiver Neoplasms - genetics - metabolism-
dc.subject.meshMicroRNAs - genetics - metabolism-
dc.subject.meshRNA, Neoplasm - genetics - metabolism-
dc.titleTwo-tiered approach identifies a network of cancer and liver disease-related genes regulated by miR-122en_HK
dc.typeArticleen_HK
dc.identifier.emailLuk, JM: jmluk@hkucc.hku.hken_HK
dc.identifier.authorityLuk, JM=rp00349en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1074/jbc.M110.196451en_HK
dc.identifier.pmid21402708-
dc.identifier.pmcidPMC3093880-
dc.identifier.scopuseid_2-s2.0-79955975777en_HK
dc.identifier.hkuros188156en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79955975777&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume286en_HK
dc.identifier.issue20en_HK
dc.identifier.spage18066en_HK
dc.identifier.epage18078en_HK
dc.identifier.isiWOS:000290585200068-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridBoutz, DR=6507782083en_HK
dc.identifier.scopusauthoridCollins, PJ=7402501086en_HK
dc.identifier.scopusauthoridSuresh, U=39661425000en_HK
dc.identifier.scopusauthoridLu, M=9036352400en_HK
dc.identifier.scopusauthoridRamírez, CM=39661254900en_HK
dc.identifier.scopusauthoridFernándezHernando, C=8634881600en_HK
dc.identifier.scopusauthoridHuang, Y=35558675700en_HK
dc.identifier.scopusauthoridAbreu, RDS=37060272400en_HK
dc.identifier.scopusauthoridLe, SY=7006184376en_HK
dc.identifier.scopusauthoridShapiro, BA=7402300640en_HK
dc.identifier.scopusauthoridLiu, AM=36134439500en_HK
dc.identifier.scopusauthoridLuk, JM=7006777791en_HK
dc.identifier.scopusauthoridAldred, SF=6602335040en_HK
dc.identifier.scopusauthoridTrinklein, ND=6506767060en_HK
dc.identifier.scopusauthoridMarcotte, EM=7003412942en_HK
dc.identifier.scopusauthoridPenalva, LOF=6602188332en_HK
dc.identifier.citeulike9002402-

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