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 language | English |
|---|---|
| Pages (from-to) | 3957-3966 |
| Number of pages | 10 |
| Journal | FASEB Journal |
| Volume | 23 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2009 |
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Keywords
- 3′ UTR
- Hematopoiesis
- p53 family
- Small noncoding RNAs
ASJC Scopus subject areas
- Biochemistry
- Biotechnology
- Genetics
- Molecular Biology
Cite this
The microRNA miR-92 increases proliferation of myeloid cells and by targeting p63 modulates the abundance of its isoforms. / Manni, Isabella; Artuso, Simona; Careccia, Silvia; Rizzo, Maria Giulia; Baserga, Renato; Piaggio, Giulia; Sacchi, Ada.
In: FASEB Journal, Vol. 23, No. 11, 2009, p. 3957-3966.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The microRNA miR-92 increases proliferation of myeloid cells and by targeting p63 modulates the abundance of its isoforms
AU - Manni, Isabella
AU - Artuso, Simona
AU - Careccia, Silvia
AU - Rizzo, Maria Giulia
AU - Baserga, Renato
AU - Piaggio, Giulia
AU - Sacchi, Ada
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - 3′ UTR
KW - Hematopoiesis
KW - p53 family
KW - Small noncoding RNAs
UR - http://www.scopus.com/inward/record.url?scp=70350560746&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70350560746&partnerID=8YFLogxK
U2 - 10.1096/fj.09-131847
DO - 10.1096/fj.09-131847
M3 - Article
C2 - 19608627
AN - SCOPUS:70350560746
VL - 23
SP - 3957
EP - 3966
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 11
ER -