Targeting long non-coding RNAs, an innovative therapeutic strategy to limit NASH progression – STARNASH

Evidence accumulated over the past decade shows that long non-coding RNAs (lncRNAs) are widely expressed and exert key roles in gene regulation. Recent studies have begun to unravel how the biogenesis of lncRNAs is distinct from that of mRNAs and is linked with their specific subcellular localizations and functions. Depending on their localization and their specific interactions with DNA, RNA or proteins, lncRNAs can modulate a wide range of biological functions including chromatin structure modifications, assembly and function of membraneless nuclear bodies, stability and translation of cytoplasmic mRNAs and modulation of various signaling pathways. As many of these functions ultimately affect gene expression in diverse biological and pathogenic contexts such as chronic liver disorders, the tissue-specific and condition-specific expression patterns of lncRNA suggest that these RNA species are not only potential disease biomarkers but also drug targets. In this project, based on our previous findings establishing the lncRNA DNM3OS (Dynamin-3 Opposite Strand) as a critical actor of pulmonary fibrosis, we aim to assess whether targeting this lncRNA represents a new innovative therapeutic approach to limit the progression of Non-Alcoholic SteatoHepatitis or NASH, a rapidly expanding and severe chronic liver disorder associated with scarring, using relevant in vivo and in vitro models.