The microRNA miR-92 increases proliferation of myeloid cells and by targeting p63 modulates the abundance of its isoforms

Isabella Manni, Simona Artuso, Silvia Careccia, Maria Giulia Rizzo, Renato Baserga, Giulia Piaggio, Ada Sacchi

Research output: Contribution to journalArticle

Abstract

MicroRNAs (miRs) are 21- to 23-nucleotide RNA molecules that regulate the stability or translational efficiency of target messenger RNAs of proteins involved in cell growth and apoptosis. miR-92 is part of the mir-17-92 cluster, which comprises members with an effect on cell proliferation. However, the role of miR-92 is unknown, and its targets have not been identified. Here, we describe a mechanism through which miR-92 contributes to regulate cell proliferation. Using a miR-92 synthetic double-strand oligonucleotide, we demonstrate that miR-92 increases 32D myeloid cell proliferation and 5-bromo-2-deoxyuridine (BrdU) incorporation and inhibits cell death. The effect is miR-92 specific since the miR-92 antagomir inhibits cell proliferation. Moreover, we show that miR-92 acts by modulating p63-isoform abundance through down-regulatation of endogenous ΔNp63β. Using luciferase reporters containing p63 3′UTR fragments with wild-type or mutant miR-92 complementary sites, we demonstrate that the wild-type 3′UTR is a direct target of miR-92. Finally, we observed that a miR-92-resistant ΔNp63β isoform (without 3′UTR) inhibits cell proliferation and parallels the effect of the antagomir. We conclude that one of the molecular mechanisms through which miR-92 increases cell proliferation is by negative regulation of an isoform of the cell-cycle regulator p63.

Original languageEnglish
Pages (from-to)3957-3966
Number of pages10
JournalFASEB Journal
Volume23
Issue number11
DOIs
Publication statusPublished - 2009

Keywords

  • 3′ UTR
  • Hematopoiesis
  • p53 family
  • Small noncoding RNAs

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

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