Long non-coding RNAs in SSc

​Fibrosis is the most severe process in the pathophysiology of SSc. The tissue is replaced with a collagen rich, stiff connective tissue leading to dysfunction and failure of affected organs (1). Long non-coding RNAs (lncRNAs) are a recently emerging class of important gene regulators mediating their effects via a wide variety of mechanisms. LncRNAs are thought to be higher in numbers than coding RNAs, underlining their potential as master regulators of biological pathways and mediators of diseases (2). However, little is known about the role of lncRNAs in fibrotic diseases.

lncRNA.jpg Hu W et al., EMBO reports, 2012

We hypothesize that lncRNAs might be key drivers in the pathophysiology of fibrosis in SSc. Therefore, lncRNA characterization might shed lights on novel fibrotic molecular mechanism. Here, we aim to identify uncharacterized lncRNAs using different screening technique like whole genome RNA sequencing or RT-qPCR on SSc vs healthy skin biopsies or fibroblasts. Furthermore, we aim to define the fibrotic molecular cascades that trigger lncRNAs dysregulation. In parallel, using gain and loss of function technologies and functional assay, we will address the role of the newly identified lncRNAs. New high-throughput, cutting-edge techniques like ATAC-seq, ChiRP or RNA pull down will be use to asses lncRNAs interactome and define the molecular mechanism of action (3,4).

  1. Gabrielli A, Avvedimento E V, Krieg T. Scleroderma. N Engl J Med. Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.; 2009 Jan;360(19):1989–2003.
  2. Cech TR, Steitz JA. The noncoding RNA revolution - Trashing old rules to forge new ones. Cell. 2014. p. 77–94.
  3. Buenrostro JD, Giresi PG, Zaba LC, Chang HY, Greenleaf WJ. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat Methods. 2013;10(12):1213–8.
  4. Chu C, Spitale RC, Chang HY. Technologies to probe functions and mechanisms of long noncoding RNAs. Nat Struct Mol Biol. 2015;22(1):29–35.

 


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