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Article: Role of miR-143 regulating DNA methyltransferases 3A in breast cancer
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TitleRole of miR-143 regulating DNA methyltransferases 3A in breast cancer
 
AuthorsNg, E
Kwong, A
Tsang, W
Leung, C
Wong, C
Kwok, T
Ma, E
 
KeywordsMedical sciences
Oncology
 
Issue Date2010
 
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
 
CitationCancer Research, 2010, v. 69 n. 24, suppl.: abstract no. 3148 [How to Cite?]
DOI: http://dx.doi.org/10.1158/0008-5472.SABCS-09-3148
 
AbstractBackground and Aims: 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 particular, decreased expression of miR-143 has been reported in various human cancers including colorectal cancer and B-cell lymphomas. The aim of this study was to elucidate the role of miR-143 dysregulation in breast cancer.Methods: Expression levels of human mature microRNAs (miRNAs) were compared with paired breast carcinomas and adjacent normal tissues by TaqMan real-time PCR based expression arrays. Decreased expression of miR-143 was further confirmed in breast cancer cell lines and paired breast tumors and normal adjacent tissues by qRT-PCR. Potential targets of miR-143 were defined. The functional effect of miR-143 and its targets was performed in human breast cancer cell lines to confirm target association.Results: Down-regulation of miR-143 was verified in both human breast cancer cell lines and 80% (12/15) of breast tumors (P < 0.001). DNA methyltranferase 3A (DNMT3A), one of a key enzyme involved in DNA methylation, was defined as a potential target of miR-143 by in-silico analysis. Overexpression of miR-143 in breast cancer cell lines down-regulated expression of DNMT3A, decreased tumor cell growth by MTT assay and soft agar colony formation assay. DNMT3A was demonstrated to be a direct target of miR-143 by luciferase reporter assay. Inverse correlation between DNMT3A protein and miR-143 was found in tumor and normal breast tissues.Conclusions: In this study, we show for the first time in breast cancer that miR-143 specifically targeted DNMT3A and the expression of miR-143 was inversely correlated with DNMT3A expression. Our findings demonstrated that down-regulation of miR-143 and up-regulation of DNMT3A are significant changes in breast tumors. These findings indicate a tumor suppressive role of miR-143 in epigenetic aberration of breast cancer.
 
ISSN0008-5472
2013 Impact Factor: 9.284
2013 SCImago Journal Rankings: 5.627
 
DOIhttp://dx.doi.org/10.1158/0008-5472.SABCS-09-3148
 
DC FieldValue
dc.contributor.authorNg, E
 
dc.contributor.authorKwong, A
 
dc.contributor.authorTsang, W
 
dc.contributor.authorLeung, C
 
dc.contributor.authorWong, C
 
dc.contributor.authorKwok, T
 
dc.contributor.authorMa, E
 
dc.date.accessioned2010-10-31T12:55:44Z
 
dc.date.available2010-10-31T12:55:44Z
 
dc.date.issued2010
 
dc.description.abstractBackground and Aims: 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 particular, decreased expression of miR-143 has been reported in various human cancers including colorectal cancer and B-cell lymphomas. The aim of this study was to elucidate the role of miR-143 dysregulation in breast cancer.Methods: Expression levels of human mature microRNAs (miRNAs) were compared with paired breast carcinomas and adjacent normal tissues by TaqMan real-time PCR based expression arrays. Decreased expression of miR-143 was further confirmed in breast cancer cell lines and paired breast tumors and normal adjacent tissues by qRT-PCR. Potential targets of miR-143 were defined. The functional effect of miR-143 and its targets was performed in human breast cancer cell lines to confirm target association.Results: Down-regulation of miR-143 was verified in both human breast cancer cell lines and 80% (12/15) of breast tumors (P < 0.001). DNA methyltranferase 3A (DNMT3A), one of a key enzyme involved in DNA methylation, was defined as a potential target of miR-143 by in-silico analysis. Overexpression of miR-143 in breast cancer cell lines down-regulated expression of DNMT3A, decreased tumor cell growth by MTT assay and soft agar colony formation assay. DNMT3A was demonstrated to be a direct target of miR-143 by luciferase reporter assay. Inverse correlation between DNMT3A protein and miR-143 was found in tumor and normal breast tissues.Conclusions: In this study, we show for the first time in breast cancer that miR-143 specifically targeted DNMT3A and the expression of miR-143 was inversely correlated with DNMT3A expression. Our findings demonstrated that down-regulation of miR-143 and up-regulation of DNMT3A are significant changes in breast tumors. These findings indicate a tumor suppressive role of miR-143 in epigenetic aberration of breast cancer.
 
dc.identifier.citationCancer Research, 2010, v. 69 n. 24, suppl.: abstract no. 3148 [How to Cite?]
DOI: http://dx.doi.org/10.1158/0008-5472.SABCS-09-3148
 
dc.identifier.doihttp://dx.doi.org/10.1158/0008-5472.SABCS-09-3148
 
dc.identifier.hkuros181442
 
dc.identifier.issn0008-5472
2013 Impact Factor: 9.284
2013 SCImago Journal Rankings: 5.627
 
dc.identifier.issue24 suppl: abstract no. 3148
 
dc.identifier.openurl
 
dc.identifier.urihttp://hdl.handle.net/10722/126911
 
dc.identifier.volume69
 
dc.languageeng
 
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
 
dc.relation.ispartofCancer Research
 
dc.subjectMedical sciences
 
dc.subjectOncology
 
dc.titleRole of miR-143 regulating DNA methyltransferases 3A in breast cancer
 
dc.typeArticle
 
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<contributor.author>Leung, C</contributor.author>
<contributor.author>Wong, C</contributor.author>
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<contributor.author>Ma, E</contributor.author>
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<description.abstract>Background and Aims: 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 particular, decreased expression of miR-143 has been reported in various human cancers including colorectal cancer and B-cell lymphomas. The aim of this study was to elucidate the role of miR-143 dysregulation in breast cancer.Methods: Expression levels of human mature microRNAs (miRNAs) were compared with paired breast carcinomas and adjacent normal tissues by TaqMan real-time PCR based expression arrays. Decreased expression of miR-143 was further confirmed in breast cancer cell lines and paired breast tumors and normal adjacent tissues by qRT-PCR. Potential targets of miR-143 were defined. The functional effect of miR-143 and its targets was performed in human breast cancer cell lines to confirm target association.Results: Down-regulation of miR-143 was verified in both human breast cancer cell lines and 80% (12/15) of breast tumors (P &lt; 0.001). DNA methyltranferase 3A (DNMT3A), one of a key enzyme involved in DNA methylation, was defined as a potential target of miR-143 by in-silico analysis. Overexpression of miR-143 in breast cancer cell lines down-regulated expression of DNMT3A, decreased tumor cell growth by MTT assay and soft agar colony formation assay. DNMT3A was demonstrated to be a direct target of miR-143 by luciferase reporter assay. Inverse correlation between DNMT3A protein and miR-143 was found in tumor and normal breast tissues.Conclusions: In this study, we show for the first time in breast cancer that miR-143 specifically targeted DNMT3A and the expression of miR-143 was inversely correlated with DNMT3A expression. Our findings demonstrated that down-regulation of miR-143 and up-regulation of DNMT3A are significant changes in breast tumors. These findings indicate a tumor suppressive role of miR-143 in epigenetic aberration of breast cancer.</description.abstract>
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