LncRNAs Associated with Neuronal Development and Oncogenesis Are Deregulated in SOD1-G93A Murine Model of Amyotrophic Lateral Sclerosis
Federica Rey,
Stefania Marcuzzo,
Silvia Bonanno,
Matteo Bordoni,
Toniella Giallongo,
Claudia Malacarne,
Cristina Cereda,
Gian Vincenzo Zuccotti,
Stephana Carelli
Affiliations
Federica Rey
Department of Biomedical and Clinical Sciences “L. Sacco”, University of Milan, Via Grassi 74, 20157 Milano, Italy
Stefania Marcuzzo
Neurology IV-Neuroimmunology and Neuromuscular Diseases Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy
Silvia Bonanno
Neurology IV-Neuroimmunology and Neuromuscular Diseases Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy
Matteo Bordoni
Centro di Eccellenza Sulle Malattie Neurodegenerative, Dipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Università Degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy
Toniella Giallongo
Department of Biomedical and Clinical Sciences “L. Sacco”, University of Milan, Via Grassi 74, 20157 Milano, Italy
Claudia Malacarne
Neurology IV-Neuroimmunology and Neuromuscular Diseases Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy
Cristina Cereda
Genomic and Post-Genomic Center, IRCCS Mondino Foundation, 27100 Pavia, Italy
Gian Vincenzo Zuccotti
Department of Biomedical and Clinical Sciences “L. Sacco”, University of Milan, Via Grassi 74, 20157 Milano, Italy
Stephana Carelli
Department of Biomedical and Clinical Sciences “L. Sacco”, University of Milan, Via Grassi 74, 20157 Milano, Italy
Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease caused in 10% of cases by inherited mutations considered “familial”. An ever-increasing amount of evidence is showing a fundamental role for RNA metabolism in ALS pathogenesis, and long non-coding RNAs (lncRNAs) appear to play a role in ALS development. Here, we aim to investigate the expression of a panel of lncRNAs (linc-Enc1, linc–Brn1a, linc–Brn1b, linc-p21, Hottip, Tug1, Eldrr, and Fendrr) which could be implicated in early phases of ALS. Via Real-Time PCR, we assessed their expression in a murine familial model of ALS (SOD1-G93A mouse) in brain and spinal cord areas of SOD1-G93A mice in comparison with that of B6.SJL control mice, in asymptomatic (week 8) and late-stage disease (week 18). We highlighted a specific area and pathogenetic-stage deregulation in each lncRNA, with linc-p21 being deregulated in all analyzed tissues. Moreover, we analyzed the expression of their human homologues in SH-SY5Y-SOD1-WT and SH-SY5Y-SOD1-G93A, observing a profound alteration in their expression. Interestingly, the lncRNAs expression in our ALS models often resulted opposite to that observed for the lncRNAs in cancer. These evidences suggest that lncRNAs could be novel disease-modifying agents, biomarkers, or pathways affected by ALS neurodegeneration.
