Background Long non-coding RNAs (lncRNAs), a class of newfound noncoding RNAs greater than 200 nucleotides in length, are prevalently transcribed in the genome [1] and have been found of crucial functional importance for disease [2]. However, the potential roles of lncRNAs in dermatomyositis (DM) are poorly understood.

Objectives The aim of this study was to determine whether lncRNAs are differentially expressed in DM patients, and to investigate the expression pattern of lncRNAs in relation to mRNA expression profile.

Methods Total RNA was extracted from muscle tissue of 15 DM patients and 5 healthy controls. An lncRNA-mRNA microarray analysis was employed to determine the expression profile of lncRNA and mRNA. Bioinformatics prediction was applied to delineate the functional roles of the differentially expressed lncRNAs. Quantitative real-time PCR (qRT-PCR) analysis was conducted to validate the expression levels of several lncRNAs and mRNAs. Statistical analysis was performed using SPSS V.16.0. A P value equal to or less than 0.05 was considered statistically significant.

Results Using microarray analysis, we identified a total of 1198 lncRNAs and 1213 mRNAs were significantly differentially expressed in DM patients compared with the healthy control group (fold change>2, P<0.05, FDR<0.05). Among them, 322 lncRNAs and 665 mRNAs were upregulated, while 876 lncRNAs and 548 mRNAs were found to be downregulated. Subgrouping DM patients according to the presence of interstitial lung disease (ILD) and anti-Jo-1 antibody revealed different expression patterns of lncRNAs, suggesting aberrantly expressed lncRNAs may be associated with ILD and anti-Jo-1 antibody. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated 10 pathways, including Systemic lupus erythematosus (ko05322), Cytokine-cytokine receptor interaction (ko04060), Toll-like receptor signaling pathway (ko04620), Osteoclast differentiation (ko04380). LncRNA-mRNA co-expression network was constructed for all significantly changed lncRNAs, which may be used for predicting target genes of lncRNAs. The results of target gene predicting revealed that the expression of 14 lncRNAs was significantly correlated to their nearby coding genes and may probably tareted to these coding genes. Interestingly, we found that the expression of lncRNA p33629 was significantly associated with highly expressed IFN-stimulated gene 15 (ISG15) and ubiquitin specific peptidase 18 (USP18) genes, which contribute to the type I interferon pathway.

Conclusions In conclusion, this is the first study demonstrated the lncRNA expression profile in muscle tissue of DM patients. We identified a series of DM associated lncRNAs, notably several lncRNAs probably invovled in the type I interferon pathway. Our findings of significantly changed expression pattern of lncRNAs indicated potential role of lncRNAs in DM and provided novel insights into the pathogenesis of DM.

References

1. Brosnan CA, Voinnet O: The long and the short of noncoding RNAs. Curr Opin Cell Biol. 2009;21(3):416-25.

2. Batista PJ, Chang HY. Long noncoding RNAs: cellular address codes in development and disease. Cell. 2013;152(6):1298-307.

Disclosure of Interest None declared