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.

Lena, A.m., Mancini, M., Rivetti di Val Cervo, P., Saintigny, G., Mahé, C., Melino, G., et al. (2012). MicroRNA-191 triggers keratinocytes senescence by SATB1 and CDK6 downregulation. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 423(3), 509-514 [10.1016/j.bbrc.2012.05.153].

MicroRNA-191 triggers keratinocytes senescence by SATB1 and CDK6 downregulation

LENA, ANNA MARIA;MELINO, GENNARO;CANDI, ELEONORA
2012-07-06

Abstract

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.
6-lug-2012
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/11 - BIOLOGIA MOLECOLARE
English
Con Impact Factor ISI
Matrix Attachment Region Binding Proteins; MicroRNAs; Gene Silencing; Humans; Cyclin-Dependent Kinase 6; Base Sequence; Down-Regulation; Cell Aging; Molecular Sequence Data; 3' Untranslated Regions; Keratinocytes; Cell Cycle; Cell Line
Lena, A.m., Mancini, M., Rivetti di Val Cervo, P., Saintigny, G., Mahé, C., Melino, G., et al. (2012). MicroRNA-191 triggers keratinocytes senescence by SATB1 and CDK6 downregulation. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 423(3), 509-514 [10.1016/j.bbrc.2012.05.153].
Lena, Am; Mancini, M; Rivetti di Val Cervo, P; Saintigny, G; Mahé, C; Melino, G; Candi, E
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/78439
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