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p63-microRNA feedback in keratinocyte senescence

Pia Rivetti di Val Cervo, Anna Maria Lena, Milena Nicoloso, Simona Rossi, Mara Mancini, HuiQing Zhou, Gaelle Saintigny, Elena Dellambra, Teresa Odorisio and Christian Mahé, et al. (2012) PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 109(4). p.1133-1138
abstract
We investigated the expression of microRNAs (miRNAs) associated with replicative senescence in human primary keratinocytes. A cohort of miRNAs up-regulated in senescence was identified by genome-wide miRNA profiling, and their change in expression was validated in proliferative versus senescent cells. Among these, miRNA (miR)-138, -181a, -181b, and -130b expression increased with serial passages. miR-138, -181a, and -181b, but not miR-130b, overexpression in proliferating cells was sufficient per se to induce senescence, as evaluated by inhibition of BrdU incorporation and quantification of senescence-activated beta-galactosidase staining. We identified Sirt1 as a direct target of miR-138, -181a, and -181b, whereas Delta Np63 expression was inhibited by miR-130b. We also found that Delta Np63 alpha inhibits miR-138, -181a, -181b, and -130b expression by binding directly to p63-responsive elements located in close proximity to the genomic loci of these miRNAs in primary keratinocytes. These findings suggest that changes in miRNA expression, by modulating the levels of regulatory proteins such as p63 and Sirt1, strongly contribute to induction of senescence in primary human keratinocytes, thus linking these two proteins. Our data also indicate that suppression of miR-138, -181a, -181b, and -130b expression is part of a growth-promoting strategy of Delta Np63 alpha in epidermal proliferating cells.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
IN-VIVO, P63, P53 HOMOLOG, PROMOTES DIFFERENTIATION, CELLULAR SENESCENCE, CELLS, SKIN, MORPHOGENESIS, METASTASIS, TELOMERASE
journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Proc. Natl. Acad. Sci. USA
volume
109
issue
4
pages
1133 - 1138
Web of Science type
Article
Web of Science id
000299412600032
JCR category
MULTIDISCIPLINARY SCIENCES
JCR impact factor
9.737 (2012)
JCR rank
4/56 (2012)
JCR quartile
1 (2012)
ISSN
0027-8424
DOI
10.1073/pnas.1112257109
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
3006995
handle
http://hdl.handle.net/1854/LU-3006995
date created
2012-10-04 17:39:00
date last changed
2012-10-09 14:44:18
@article{3006995,
  abstract     = {We investigated the expression of microRNAs (miRNAs) associated with replicative senescence in human primary keratinocytes. A cohort of miRNAs up-regulated in senescence was identified by genome-wide miRNA profiling, and their change in expression was validated in proliferative versus senescent cells. Among these, miRNA (miR)-138, -181a, -181b, and -130b expression increased with serial passages. miR-138, -181a, and -181b, but not miR-130b, overexpression in proliferating cells was sufficient per se to induce senescence, as evaluated by inhibition of BrdU incorporation and quantification of senescence-activated beta-galactosidase staining. We identified Sirt1 as a direct target of miR-138, -181a, and -181b, whereas Delta Np63 expression was inhibited by miR-130b. We also found that Delta Np63 alpha inhibits miR-138, -181a, -181b, and -130b expression by binding directly to p63-responsive elements located in close proximity to the genomic loci of these miRNAs in primary keratinocytes. These findings suggest that changes in miRNA expression, by modulating the levels of regulatory proteins such as p63 and Sirt1, strongly contribute to induction of senescence in primary human keratinocytes, thus linking these two proteins. Our data also indicate that suppression of miR-138, -181a, -181b, and -130b expression is part of a growth-promoting strategy of Delta Np63 alpha in epidermal proliferating cells.},
  author       = {Cervo, Pia Rivetti di Val and Lena, Anna Maria and Nicoloso, Milena and Rossi, Simona and Mancini, Mara and Zhou, HuiQing and Saintigny, Gaelle and Dellambra, Elena and Odorisio, Teresa and Mah{\'e}, Christian and Calin, George Adrian and Candi, Eleonora and Melino, Gennaro},
  issn         = {0027-8424},
  journal      = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
  keyword      = {IN-VIVO,P63,P53 HOMOLOG,PROMOTES DIFFERENTIATION,CELLULAR SENESCENCE,CELLS,SKIN,MORPHOGENESIS,METASTASIS,TELOMERASE},
  language     = {eng},
  number       = {4},
  pages        = {1133--1138},
  title        = {p63-microRNA feedback in keratinocyte senescence},
  url          = {http://dx.doi.org/10.1073/pnas.1112257109},
  volume       = {109},
  year         = {2012},
}

Chicago
Cervo, Pia Rivetti di Val, Anna Maria Lena, Milena Nicoloso, Simona Rossi, Mara Mancini, HuiQing Zhou, Gaelle Saintigny, et al. 2012. “p63-microRNA Feedback in Keratinocyte Senescence.” Proceedings of the National Academy of Sciences of the United States of America 109 (4): 1133–1138.
APA
Cervo, P. R. di V., Lena, A. M., Nicoloso, M., Rossi, S., Mancini, M., Zhou, H., Saintigny, G., et al. (2012). p63-microRNA feedback in keratinocyte senescence. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 109(4), 1133–1138.
Vancouver
1.
Cervo PR di V, Lena AM, Nicoloso M, Rossi S, Mancini M, Zhou H, et al. p63-microRNA feedback in keratinocyte senescence. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2012;109(4):1133–8.
MLA
Cervo, Pia Rivetti di Val, Anna Maria Lena, Milena Nicoloso, et al. “p63-microRNA Feedback in Keratinocyte Senescence.” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 109.4 (2012): 1133–1138. Print.