title: p53 Represses the Oncogenic Sno-MiR-28 Derived from a SnoRNA.
abstract: p53 is a master tumour repressor that participates in vast regulatory networks, including feedback loops involving microRNAs (miRNAs) that regulate p53 and that themselves are direct p53 transcriptional targets. We show here that a group of polycistronic miRNA-like non-coding RNAs derived from small nucleolar RNAs (sno-miRNAs) are transcriptionally repressed by p53 through their host gene, SNHG1. The most abundant of these, sno-miR-28, directly targets the p53-stabilizing gene, TAF9B. Collectively, p53, SNHG1, sno-miR-28 and TAF9B form a regulatory loop which affects p53 stability and downstream p53-regulated pathways. In addition, SNHG1, SNORD28 and sno-miR-28 are all significantly upregulated in breast tumours and the overexpression of sno-miR-28 promotes breast epithelial cell proliferation. This research has broadened our knowledge of the crosstalk between small non-coding RNA pathways and roles of sno-miRNAs in p53 regulation.
authors.affiliation: Centre for Personalized Cancer Medicine, University of Adelaide, Adelaide, SA, Australia; Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia; Centre for Cancer Biology, SA Pathology, Adelaide, SA, Australia.
authors.forename: Feng
authors.initials: F
authors.lastname: Yu
authors.affiliation: Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia; Centre for Cancer Biology, SA Pathology, Adelaide, SA, Australia.
authors.forename: Cameron P
authors.initials: CP
authors.lastname: Bracken
authors.affiliation: ACRF Cancer Genomics Facility, Centre for Cancer Biology, SA Pathology, Adelaide, Australia; School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Pillman
authors.affiliation: ACRF Cancer Genomics Facility, Centre for Cancer Biology, SA Pathology, Adelaide, Australia; School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Lawrence
authors.affiliation: Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia; Centre for Cancer Biology, SA Pathology, Adelaide, SA, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Goodall
authors.affiliation: Centre for Personalized Cancer Medicine, University of Adelaide, Adelaide, SA, Australia; Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia.
authors.forename: David F
authors.initials: DF
authors.lastname: Callen
authors.affiliation: Centre for Personalized Cancer Medicine, University of Adelaide, Adelaide, SA, Australia; Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia; Swinburne University of Technology, Kuching, Sarawak, Malaysia.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Neilsen
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D020537:RNA, Small Nucleolar / Q000378:metabolism*; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics*; D035362:Transcription Factor TFIID / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: C570628:MIRN28 microRNA, human; D035683:MicroRNAs; D020537:RNA, Small Nucleolar; C502209:TAF9b protein, human; D035381:TATA-Binding Protein Associated Factors; C495901:TP53 protein, human; D035362:Transcription Factor TFIID; D016159:Tumor Suppressor Protein p53