p53 Represses the Oncogenic Sno-MiR-28 Derived from a SnoRNA

Feng Yu; Cameron P Bracken; Katherine A Pillman; David M Lawrence; Gregory J Goodall; David F Callen; Paul M Neilsen

doi:10.1371/journal.pone.0129190

p53 Represses the Oncogenic Sno-MiR-28 Derived from a SnoRNA

PLoS One. 2015 Jun 10;10(6):e0129190. doi: 10.1371/journal.pone.0129190. eCollection 2015.

Authors

Feng Yu¹, Cameron P Bracken², Katherine A Pillman³, David M Lawrence³, Gregory J Goodall², David F Callen⁴, Paul M Neilsen⁵

Affiliations

¹ 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.
² Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia; Centre for Cancer Biology, SA Pathology, Adelaide, SA, Australia.
³ ACRF Cancer Genomics Facility, Centre for Cancer Biology, SA Pathology, Adelaide, Australia; School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia.
⁴ Centre for Personalized Cancer Medicine, University of Adelaide, Adelaide, SA, Australia; Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia.
⁵ 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms / genetics*
Breast Neoplasms / metabolism
Breast Neoplasms / pathology
Cell Line, Tumor
Cell Proliferation
Female
Gene Expression Regulation, Neoplastic
HCT116 Cells
Humans
MicroRNAs / genetics*
RNA, Small Nucleolar / metabolism*
TATA-Binding Protein Associated Factors / genetics*
Transcription Factor TFIID / genetics*
Tumor Suppressor Protein p53 / metabolism*

Substances

MIRN28 microRNA, human
MicroRNAs
RNA, Small Nucleolar
TAF9b protein, human
TATA-Binding Protein Associated Factors
TP53 protein, human
Transcription Factor TFIID
Tumor Suppressor Protein p53

Associated data

BioProject/PRJNA257235
SRA/SRP045204

Grants and funding

This research received funding from National Health and Medical Research Council of Australia (NHMRC) grant 44112162, NHMRC grant GNT1034633 (http://www.nhmrc.gov.au), and from the National Breast Cancer Foundation Australia (http://www.nbcf.org.au), all assigned to DC. CB is supported by a Fellowship from the National Breast Cancer Foundation Australia, and FY is supported by Adelaide Scholarships International (http://www.adelaide.edu.au).