Background Systemic sclerosis (SSc) is an autoimmune disease characterised by fibrosis of skin and multiple organs of which pathogenesis is poorly understood. Here we studied differentially expressed coding and non-coding genes in relation to SSc pathogenesis with a specific focus on antisense non-coding RNAs.
Materials and methods Skin biopsy-derived RNAs from fourteen early SSc patients and six healthy individuals were sequenced with ion-torrent and analysed using DEseq2. Protein-coding and non-coding genes annotated in GENCODEV7 were analysed. Significant long non-coding RNAs were independently replicated in a Northern American dataset.
Results 4901 genes with a fold change >1.5 and a false discovery rate of less than 5% were detected in patients versus controls. Upregulated coding genes clustered in immunological, cell adhesion and keratin-related processes as previously found by microarray studies. Interestingly, 676 deregulated non-coding genes were detected, 257 of which were classified as antisense genes. 42% of these antisense genes had a concurrent deregulated sense gene. The majority of the sense-antisense genes had a similar effect sizes in an independent North American dataset with three genes (OTUD6B-AS1, CTBP1-AS2 and HMGN3-AS1) exceeding the study-wide Bonferroni-corrected ρ-value (PBonf <0.0024, Pcombined=1.6×10-9, 1.7 × 10–6, 2.6 × 10–6, respectively). Intriguingly, the correlation of sense-antisense gene pairs deregulated in SSc is stronger than sense-antisense gene pairs not deregulated in SSc (p<0.001).
Conclusions For the first time we highlight that together with coding genes, (antisense) long noncoding RNAs are deregulated in skin tissue of SSc patients suggesting a novel class of genes involved in pathogenesis of SSc.
- Systemic Sclerosis
- RNA sequencing
- antisense long noncoding RNAs.
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