Show simple item record

dc.contributor.authorWee, EJH
dc.contributor.authorPeters, K
dc.contributor.authorNair, SS
dc.contributor.authorHulf, T
dc.contributor.authorStein, S
dc.contributor.authorWagner, S
dc.contributor.authorBailey, P
dc.contributor.authorLee, SY
dc.contributor.authorQu, WJ
dc.contributor.authorBrewster, B
dc.contributor.authorFrench, JD
dc.contributor.authorDobrovic, A
dc.contributor.authorFrancis, GD
dc.contributor.authorClark, SJ
dc.contributor.authorBrown, MA
dc.date.accessioned2017-05-03T14:20:49Z
dc.date.available2017-05-03T14:20:49Z
dc.date.issued2012
dc.date.modified2013-09-09T22:47:16Z
dc.identifier.issn0950-9232
dc.identifier.doi10.1038/onc.2011.584
dc.identifier.urihttp://hdl.handle.net/10072/52982
dc.description.abstractMicroRNAs (miRNAs) are small non-coding RNAs of ~20?nt in length that are capable of modulating gene expression post-transcriptionally. Although miRNAs have been implicated in cancer, including breast cancer, the regulation of miRNA transcription and the role of defects in this process in cancer is not well understood. In this study we have mapped the promoters of 93 breast cancer-associated miRNAs, and then looked for associations between DNA methylation of 15 of these promoters and miRNA expression in breast cancer cells. The miRNA promoters with clearest association between DNA methylation and expression included a previously described and a novel promoter of the Hsa-mir-200b cluster. The novel promoter of the Hsa-mir-200b cluster, denoted P2, is located ~2?kb upstream of the 5' stemloop and maps within a CpG island. P2 has comparable promoter activity to the previously reported promoter (P1), and is able to drive the expression of miR-200b in its endogenous genomic context. DNA methylation of both P1 and P2 was inversely associated with miR-200b expression in eight out of nine breast cancer cell lines, and in vitro methylation of both promoters repressed their activity in reporter assays. In clinical samples, P1 and P2 were differentially methylated with methylation inversely associated with miR-200b expression. P1 was hypermethylated in metastatic lymph nodes compared with matched primary breast tumours whereas P2 hypermethylation was associated with loss of either oestrogen receptor or progesterone receptor. Hypomethylation of P2 was associated with gain of HER2 and androgen receptor expression. These data suggest an association between miR-200b regulation and breast cancer subtype and a potential use of DNA methylation of miRNA promoters as a component of a suite of breast cancer biomarkers.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherNature Publishing Group
dc.publisher.placeUnited Kingdom
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom4182
dc.relation.ispartofpageto4195
dc.relation.ispartofissue38
dc.relation.ispartofjournalOncogene
dc.relation.ispartofvolume31
dc.rights.retentionY
dc.subject.fieldofresearchClinical sciences
dc.subject.fieldofresearchOncology and carcinogenesis
dc.subject.fieldofresearchcode3202
dc.subject.fieldofresearchcode3211
dc.titleMapping the regulatory sequences controlling 93 breast cancer-associated miRNA genes leads to the identification of two functional promoters of the Hsa-mir-200b cluster, methylation....
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2012
gro.hasfulltextNo Full Text
gro.griffith.authorFrancis, Glenn D.


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record