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Central role of the p53 pathway in the noncoding-RNA response to oxidative stress.
Fuschi, Paola; Carrara, Matteo; Voellenkle, Christine; Garcia-Manteiga, Jose Manuel; Righini, Paolo; Maimone, Biagina; Sangalli, Elena; Villa, Francesco; Specchia, Claudia; Picozza, Mario; Nano, Giovanni; Gaetano, Carlo; Spinetti, Gaia; Puca, Annibale A; Magenta, Alessandra; Martelli, Fabio.
Afiliação
  • Fuschi P; Molecular Cardiology Laboratory, IRCCS Policlinico S. Donato, 20097, San Donato Milanese, Milan, Italy.
  • Carrara M; Molecular Cardiology Laboratory, IRCCS Policlinico S. Donato, 20097, San Donato Milanese, Milan, Italy.
  • Voellenkle C; Molecular Cardiology Laboratory, IRCCS Policlinico S. Donato, 20097, San Donato Milanese, Milan, Italy.
  • Garcia-Manteiga JM; Center for Translational Genomics and BioInformatics, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.
  • Righini P; Operative Unit of Vascular Surgery I, IRCCS Policlinico S. Donato, 20097, San Donato Milanese, Milan, Italy.
  • Maimone B; Molecular Cardiology Laboratory, IRCCS Policlinico S. Donato, 20097, San Donato Milanese, Milan, Italy.
  • Sangalli E; Cardiovascular Research Unit, IRCCS MultiMedica, 20138, Milan, Italy.
  • Villa F; Cardiovascular Research Unit, IRCCS MultiMedica, 20138, Milan, Italy.
  • Specchia C; Cardiovascular Research Unit, IRCCS MultiMedica, 20138, Milan, Italy.
  • Picozza M; Department of Molecular and Traslational Medicine, University of Brescia, 25123, Brescia, Italy.
  • Nano G; Vascular Pathology Laboratory, Istituto Dermopatico dell'Immacolata-IRCCS, FLMM, 00167, Rome, Italy.
  • Gaetano C; Operative Unit of Vascular Surgery I, IRCCS Policlinico S. Donato, 20097, San Donato Milanese, Milan, Italy.
  • Spinetti G; University of Milan, 20133, Milan, Italy.
  • Puca AA; Division of Cardiovascular Epigenetics, Department of Cardiology, Goethe University, Frankfurt am Main, 60596, Germany.
  • Magenta A; Cardiovascular Research Unit, IRCCS MultiMedica, 20138, Milan, Italy.
  • Martelli F; Cardiovascular Research Unit, IRCCS MultiMedica, 20138, Milan, Italy.
Aging (Albany NY) ; 9(12): 2559-2586, 2017 12 12.
Article em En | MEDLINE | ID: mdl-29242407
Oxidative stress plays a fundamental role in many conditions. Specifically, redox imbalance inhibits endothelial cell (EC) growth, inducing cell death and senescence. We used global transcriptome profiling to investigate the involvement of noncoding-RNAs in these phenotypes. By RNA-sequencing, transcriptome changes were analyzed in human ECs exposed to H2O2, highlighting a pivotal role of p53-signaling. Bioinformatic analysis and validation in p53-silenced ECs, identified several p53-targets among both mRNAs and long noncoding-RNAs (lncRNAs), including MALAT1 and NEAT1. Among microRNAs (miRNAs), miR-192-5p was the most induced by H2O2 treatment, in a p53-dependent manner. Down-modulated mRNA-targets of miR-192-5p were involved in cell cycle, DNA repair and stress response. Accordingly, miR-192-5p overexpression significantly decreased EC proliferation, inducing cell death. A central role of the p53-pathway was also confirmed by the analysis of differential exon usage: Upon H2O2 treatment, the expression of p53-dependent 5'-isoforms of MDM2 and PVT1 increased selectively. The transcriptomic alterations identified in H2O2-treated ECs were also observed in other physiological and pathological conditions where redox control plays a fundamental role, such as ECs undergoing replicative senescence, skeletal muscles of critical limb-ischemia patients and the peripheral-blood mononuclear cells of long-living individuals. Collectively, these findings indicate a prominent role of noncoding-RNAs in oxidative stress response.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regulação da Expressão Gênica / Proteína Supressora de Tumor p53 / Estresse Oxidativo / RNA não Traduzido Tipo de estudo: Prognostic_studies Limite: Aged / Aged80 / Female / Humans / Male Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regulação da Expressão Gênica / Proteína Supressora de Tumor p53 / Estresse Oxidativo / RNA não Traduzido Tipo de estudo: Prognostic_studies Limite: Aged / Aged80 / Female / Humans / Male Idioma: En Ano de publicação: 2017 Tipo de documento: Article