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Article: MicroRNA-143 targets DNA methyltransferases 3A in colorectal cancer

TitleMicroRNA-143 targets DNA methyltransferases 3A in colorectal cancer
Authors
KeywordsColorectal cancer
DNMT3A
MiR-143
Tumour suppressor
Issue Date2009
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/bjc
Citation
British Journal Of Cancer, 2009, v. 101 n. 4, p. 699-706 How to Cite?
AbstractBackground:MicroRNAs (miRNAs) are 19-25-nucleotides regulatory non-protein-coding RNA molecules that regulate the expressions of a wide variety of genes, including some involved in cancer development. In this study, we investigated the possible role of miR-143 in colorectal cancer (CRC).Methods:Expression levels of human mature miRNAs were examined using real-time PCR-based expression arrays on paired colorectal carcinomas and adjacent non-cancerous colonic tissues. The downregulation of miR-143 was further evaluated in colon cancer cell lines and in paired CRC and adjacent non-cancerous colonic tissues by qRT-PCR. Potential targets of miR-143 were defined. The functional effect of miR-143 and its targets was investigated in human colon cancer cell lines to confirm miRNA-target association.Results:Both real-time PCR-based expression arrays and qRT-PCR showed that miR-143 was frequently downregulated in 87.5% (35 of 40) of colorectal carcinoma tissues compared with their adjacent non-cancerous colonic tissues. Using in silico predictions, DNA methyltranferase 3A (DNMT3A) was defined as a potential target of miR-143. Restoration of the miR-143 expression in colon cell lines decreased tumour cell growth and soft-agar colony formation, and downregulated the DNMT3A expression in both mRNA and protein levels. DNMT3A was shown to be a direct target of miR-143 by luciferase reporter assay. Furthermore, the miR-143 expression was observed to be inversely correlated with DNMT3A mRNA and protein expression in CRC tissues.Conclusion:Our findings suggest that miR-143 regulates DNMT3A in CRC. These findings elucidated a tumour-suppressive role of miR-143 in the epigenetic aberration of CRC, providing a potential development of miRNA-based targeted approaches for CRC therapy. © 2009 Cancer Research UK.
Persistent Identifierhttp://hdl.handle.net/10722/92032
ISSN
2015 Impact Factor: 5.569
2015 SCImago Journal Rankings: 2.939
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grants CouncilCUHK4270/04 M
466908
467609
Strategic Investment Fund for the Institute of Digestive Disease
Chinese University of Hong Kong
Else-Kroener-Stiftung
Deutsche Krebshilfe
BMBF
Funding Information:

This work was supported by a Earmarked Grant (CUHK4270/04 M, 466908, 467609) from Hong Kong Research Grants Council, Strategic Investment Fund for the Institute of Digestive Disease, Chinese University of Hong Kong and a grant from Else-Kroener-Stiftung (Homburg, Germany), Deutsche Krebshilfe, and the BMBF.

References

 

DC FieldValueLanguage
dc.contributor.authorNg, EKOen_HK
dc.contributor.authorTsang, WPen_HK
dc.contributor.authorNg, SSMen_HK
dc.contributor.authorJin, HCen_HK
dc.contributor.authorYu, Jen_HK
dc.contributor.authorLi, JJen_HK
dc.contributor.authorRöcken, Cen_HK
dc.contributor.authorEbert, MPAen_HK
dc.contributor.authorKwok, TTen_HK
dc.contributor.authorSung, JJYen_HK
dc.date.accessioned2010-09-17T10:34:04Z-
dc.date.available2010-09-17T10:34:04Z-
dc.date.issued2009en_HK
dc.identifier.citationBritish Journal Of Cancer, 2009, v. 101 n. 4, p. 699-706en_HK
dc.identifier.issn0007-0920en_HK
dc.identifier.urihttp://hdl.handle.net/10722/92032-
dc.description.abstractBackground:MicroRNAs (miRNAs) are 19-25-nucleotides regulatory non-protein-coding RNA molecules that regulate the expressions of a wide variety of genes, including some involved in cancer development. In this study, we investigated the possible role of miR-143 in colorectal cancer (CRC).Methods:Expression levels of human mature miRNAs were examined using real-time PCR-based expression arrays on paired colorectal carcinomas and adjacent non-cancerous colonic tissues. The downregulation of miR-143 was further evaluated in colon cancer cell lines and in paired CRC and adjacent non-cancerous colonic tissues by qRT-PCR. Potential targets of miR-143 were defined. The functional effect of miR-143 and its targets was investigated in human colon cancer cell lines to confirm miRNA-target association.Results:Both real-time PCR-based expression arrays and qRT-PCR showed that miR-143 was frequently downregulated in 87.5% (35 of 40) of colorectal carcinoma tissues compared with their adjacent non-cancerous colonic tissues. Using in silico predictions, DNA methyltranferase 3A (DNMT3A) was defined as a potential target of miR-143. Restoration of the miR-143 expression in colon cell lines decreased tumour cell growth and soft-agar colony formation, and downregulated the DNMT3A expression in both mRNA and protein levels. DNMT3A was shown to be a direct target of miR-143 by luciferase reporter assay. Furthermore, the miR-143 expression was observed to be inversely correlated with DNMT3A mRNA and protein expression in CRC tissues.Conclusion:Our findings suggest that miR-143 regulates DNMT3A in CRC. These findings elucidated a tumour-suppressive role of miR-143 in the epigenetic aberration of CRC, providing a potential development of miRNA-based targeted approaches for CRC therapy. © 2009 Cancer Research UK.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/bjcen_HK
dc.relation.ispartofBritish Journal of Canceren_HK
dc.subjectColorectal canceren_HK
dc.subjectDNMT3Aen_HK
dc.subjectMiR-143en_HK
dc.subjectTumour suppressoren_HK
dc.subject.meshColorectal Neoplasms - enzymology - genetics-
dc.subject.meshDNA (Cytosine-5-)-Methyltransferase - metabolism-
dc.subject.meshGene Expression Regulation, Neoplastic - genetics-
dc.subject.meshMicroRNAs - genetics - metabolism-
dc.subject.meshCell Line, Tumor-
dc.titleMicroRNA-143 targets DNA methyltransferases 3A in colorectal canceren_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0007-0920&volume=101&issue=4&spage=699&epage=706&date=2009&atitle=MicroRNA-143+targets+DNA+methyltransferases+3A+in+colorectal+cancer-
dc.identifier.emailNg, EKO: ngko@hku.hken_HK
dc.identifier.authorityNg, EKO=rp01364en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/sj.bjc.6605195en_HK
dc.identifier.pmid19638978-
dc.identifier.pmcidPMC2736825-
dc.identifier.scopuseid_2-s2.0-68749097208en_HK
dc.identifier.hkuros168712-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-68749097208&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume101en_HK
dc.identifier.issue4en_HK
dc.identifier.spage699en_HK
dc.identifier.epage706en_HK
dc.identifier.eissn1532-1827-
dc.identifier.isiWOS:000268861000020-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridNg, EKO=21135553700en_HK
dc.identifier.scopusauthoridTsang, WP=7201558605en_HK
dc.identifier.scopusauthoridNg, SSM=26021413400en_HK
dc.identifier.scopusauthoridJin, HC=24577511700en_HK
dc.identifier.scopusauthoridYu, J=35351306800en_HK
dc.identifier.scopusauthoridLi, JJ=16637556300en_HK
dc.identifier.scopusauthoridRöcken, C=7006367084en_HK
dc.identifier.scopusauthoridEbert, MPA=35239660600en_HK
dc.identifier.scopusauthoridKwok, TT=35196382300en_HK
dc.identifier.scopusauthoridSung, JJY=35405352400en_HK
dc.identifier.citeulike5317002-

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