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The microRNA miR‐92 increases proliferation of myeloid cells and by targeting p63 modulates the abundance of its isoforms
Author(s) -
Manni Isabella,
Artuso Simona,
Careccia Silvia,
Giulia Rizzo Maria,
Baserga Renato,
Piaggio Giulia,
Sacchi Ada
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-131847
Subject(s) - microrna , cell growth , antagomir , gene isoform , microbiology and biotechnology , three prime untranslated region , untranslated region , biology , cell cycle , cell , messenger rna , genetics , gene
MicroRNAs (miRs) are 21‐ to 23‐nucleo‐tide RNA molecules that regulate the stability or trans‐lational 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 ΔNp6β. 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.—Manni, I., Artuso, S., Careccia, S., Rizzo, M. G., Baserga, R., Piaggio, G., Sacchi, A. The microRNA miR‐92 increases proliferation of myeloid cells and by targeting p63 modulates the abundance of its isoforms. FASEBJ. 23, 3957‐3966 (2009). www.fasebj.org