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
PLoS One, 2015;10(6):e0129190.
PMID: 26061048 DOI: 10.1371/journal.pone.0129190

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.