Landscape of Long Noncoding RNAs in Psoriatic and Healthy Skin

Abstract

We used RNA sequencing to study and characterize the long noncoding RNA (lncRNA) transcriptome in lesional skin from psoriasis patients before (PP) and after treatment (PT) with adalimumab and in normal skin from healthy individuals (NN). To this end, we sequenced total RNA from 18 psoriasis patients and 16 healthy controls. We merged three lncRNA reference datasets to create a single combined reference of 67,157 lncRNA transcripts with no overlaps. We identified differential expression of 971 lncRNAs between PP and NN, 157 between PP and PT, and 377 between PT and NN. Using differentially expressed lncRNAs between PP and NN, we identified a molecular lncRNA signature that distinguishes psoriatic skin from healthy skin. Furthermore, we performed an unsupervised hierarchical analysis that revealed distinct clustering of PP samples from NN. A coding noncoding network analysis revealed a large network of highly correlated lncRNA and protein coding transcripts that provided insight into the potential functions of unannotated lncRNAs. To the best of our knowledge, this description of both polyadenylated as well as nonpolyadenylated lncRNA transcripts in psoriasis has not been previously reported. Our findings highlight the potential importance of lncRNAs in the biology of psoriasis and response to treatment.

Conflict of interest statement

Conflict of Interest

The authors state no conflict of interest.

Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1. Heatmap of differentially expressed transcripts between PP and NN skin

Differentially regulated transcripts between PP and NN skin (n=971) are shown in a heatmap image. The green color indicates high expression levels whereas red indicates low expression levels. The black bar above the heatmap indicates NN skin and the purple bar above the heatmap indicates PP skin. Note that the number of upregulated transcripts is more than the number of downregulated transcripts in PP.

Figure 2. Unsupervised hierarchical clustering of transcripts expressed in PP and NN skin

Figure 3

a: Number of differentially expressed lncRNA transcripts in three comparisons, PP vs NN, PP vs PT and PT vs NN. b: LncRNA molecular distance to health analysis of PP and PT using NN as baseline. Molecular distance to health (MDTH) for PP and PT is shown. Expression levels of NN were used as baseline. Note that PP skin has higher MDTH than PT.