Fiche publication
Date publication
avril 2021
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
Auteurs
Membres identifiés du Cancéropôle Est :
Dr RAFFELSBERGER Wolfgang
,
Dr THOMPSON Julie
Tous les auteurs :
Djeddi S, Reiss D, Menuet A, Freismuth S, de Carvalho Neves J, Djerroud S, Massana-Muñoz X, Sosson AS, Kretz C, Raffelsberger W, Keime C, Dorchies OM, Thompson J, Laporte J
Lien Pubmed
Résumé
Omics analyses are powerful methods to obtain an integrated view of complex biological processes, disease progression or therapy efficiency. However, few studies have compared different disease forms and different therapy strategies to define the common molecular signatures representing the most significant implicated pathways. Here, we used RNA sequencing and mass spectrometry data to profile the transcriptomes and proteomes of mouse models for three forms of centronuclear myopathies (CNM), untreated or treated with either a drug (tamoxifen), antisense oligonucleotides reducing the level of dynamin 2 (DNM2), or following modulation of dynamin 2 or amphiphysin 2 (BIN1) through genetic crosses. Unsupervised analysis and differential gene and protein expression were performed to retrieve CNM molecular signatures. Longitudinal studies before, at and after disease onset highlighted potential disease causes and consequences. Main pathways in the common CNM disease signature include muscle contraction, regeneration and inflammation. The common therapy signature revealed novel potential therapeutic targets including the calcium regulator sarcolipin. We identified several novel biomarkers validated in muscle and/or plasma through RNA quantification, western blotting and ELISA assays, including ANXA2 and IGFBP2. This study validates the concept of using multi-omics approaches to identify molecular signatures common to different disease forms and therapeutic strategies.
Référence
Mol Ther. 2021 Apr 30;:
