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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.
Keywords
IN-VIVO, P63, P53 HOMOLOG, PROMOTES DIFFERENTIATION, CELLULAR SENESCENCE, CELLS, SKIN, MORPHOGENESIS, METASTASIS, TELOMERASE

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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.
@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},
  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},
}

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