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MicroRNA-191 triggers keratinocytes senescence by SATB1 and CDK6 downregulation

Keratinocyte replicative senescence has an important role in time-dependent changes of the epidermis, a tissue with high turnover. Senescence encompasses growth arrest during which cells remain metabolically active but acquire a typical enlarged, vacuolar and flattened morphology. It is also accompa...

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Detalles Bibliográficos
Autores principales: Lena, A.M., Mancini, M., Rivetti di Val Cervo, P., Saintigny, G., Mahé, C., Melino, G., Candi, E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Academic Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400053/
https://www.ncbi.nlm.nih.gov/pubmed/22683624
http://dx.doi.org/10.1016/j.bbrc.2012.05.153
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author Lena, A.M.
Mancini, M.
Rivetti di Val Cervo, P.
Saintigny, G.
Mahé, C.
Melino, G.
Candi, E.
author_facet Lena, A.M.
Mancini, M.
Rivetti di Val Cervo, P.
Saintigny, G.
Mahé, C.
Melino, G.
Candi, E.
author_sort Lena, A.M.
collection PubMed
description Keratinocyte replicative senescence has an important role in time-dependent changes of the epidermis, a tissue with high turnover. Senescence encompasses growth arrest during which cells remain metabolically active but acquire a typical enlarged, vacuolar and flattened morphology. It is also accompanied by the expression of endogenous senescence-associated-β-galactosidase and specific gene expression profiles. MicroRNAs levels have been shown to be modulated during keratinocytes senescence, playing key roles in inhibiting proliferation and in the acquisition of senescent markers. Here, we identify miR-191 as an anti-proliferative and replicative senescence-associated miRNA in primary human keratinocytes. Its overexpression is sufficient per se to induce senescence, as evaluated by induction of several senescence-associated markers. We show that SATB1 and CDK6 3′UTRs are two miR-191 direct targets involved in this pathway. Cdk6 and Satb1 protein levels decrease during keratinocytes replicative senescence and their silencing by siRNA is able to induce a G1 block in cell cycle, accompanied by an increase in senescence-associated markers.
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spelling pubmed-34000532012-07-24 MicroRNA-191 triggers keratinocytes senescence by SATB1 and CDK6 downregulation Lena, A.M. Mancini, M. Rivetti di Val Cervo, P. Saintigny, G. Mahé, C. Melino, G. Candi, E. Biochem Biophys Res Commun Article Keratinocyte replicative senescence has an important role in time-dependent changes of the epidermis, a tissue with high turnover. Senescence encompasses growth arrest during which cells remain metabolically active but acquire a typical enlarged, vacuolar and flattened morphology. It is also accompanied by the expression of endogenous senescence-associated-β-galactosidase and specific gene expression profiles. MicroRNAs levels have been shown to be modulated during keratinocytes senescence, playing key roles in inhibiting proliferation and in the acquisition of senescent markers. Here, we identify miR-191 as an anti-proliferative and replicative senescence-associated miRNA in primary human keratinocytes. Its overexpression is sufficient per se to induce senescence, as evaluated by induction of several senescence-associated markers. We show that SATB1 and CDK6 3′UTRs are two miR-191 direct targets involved in this pathway. Cdk6 and Satb1 protein levels decrease during keratinocytes replicative senescence and their silencing by siRNA is able to induce a G1 block in cell cycle, accompanied by an increase in senescence-associated markers. Academic Press 2012-07-06 /pmc/articles/PMC3400053/ /pubmed/22683624 http://dx.doi.org/10.1016/j.bbrc.2012.05.153 Text en © 2012 Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/3.0/ Open Access under CC BY-NC-ND 3.0 (https://creativecommons.org/licenses/by-nc-nd/3.0/) license
spellingShingle Article
Lena, A.M.
Mancini, M.
Rivetti di Val Cervo, P.
Saintigny, G.
Mahé, C.
Melino, G.
Candi, E.
MicroRNA-191 triggers keratinocytes senescence by SATB1 and CDK6 downregulation
title MicroRNA-191 triggers keratinocytes senescence by SATB1 and CDK6 downregulation
title_full MicroRNA-191 triggers keratinocytes senescence by SATB1 and CDK6 downregulation
title_fullStr MicroRNA-191 triggers keratinocytes senescence by SATB1 and CDK6 downregulation
title_full_unstemmed MicroRNA-191 triggers keratinocytes senescence by SATB1 and CDK6 downregulation
title_short MicroRNA-191 triggers keratinocytes senescence by SATB1 and CDK6 downregulation
title_sort microrna-191 triggers keratinocytes senescence by satb1 and cdk6 downregulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400053/
https://www.ncbi.nlm.nih.gov/pubmed/22683624
http://dx.doi.org/10.1016/j.bbrc.2012.05.153
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