Canonical and Interior Circular RNAs Function as Competing Endogenous RNAs in Psoriatic Skin.

Xiaoxin Liu,Weixiong Zhang,Jacqueline Frost,Anne Bowcock

doi:10.3390/ijms22105182

Abstract

(1) Background: Understanding the function of circular RNAs (circRNAs), a class of noncoding RNA, in psoriatic skin can provide important insights into the complex regulation of genes contributing to the pathogenesis of psoriasis. (2) Methods: A novel method was applied to RNA-seq datasets from 93 skin biopsy samples to comprehensively identify circRNAs of all types, i.e., canonical circRNAs from the intron-exon junctions of mRNAs and interior circRNAs (i-circRNAs) from the interior regions of exons, introns, and intergenic regions. Selected circRNAs were experimentally validated by qRT-PCR and Sanger sequencing. CircRNAs with abundant and differential expression were identified and their putative function as competing endogenous RNAs (ceRNAs) was analyzed by an integrated analysis of circRNAs, microRNAs, and mRNAs. (3) Results: With a comprehensive search using no information of splicing signals, we systematically identified 179 highly abundant circRNAs in psoriatic skin. Many of these were reported for the first time and many were differentially expressed in involved versus normal or uninvolved skin. Validation based on three additional RNA-seq datasets confirmed most of the identified circRNAs in psoriatic skin. Experimental analyses confirmed the expression of the well-known circRNA CDR1as, a canonical circRNA, and a novel i-circRNA in psoriasis. We also identified many circRNAs that may act as ceRNAs to regulate the expression of mRNA genes in psoriasis-related signaling pathways in psoriasis. (4) Conclusions: The result of the study suggested that circRNAs are abundant in psoriatic skin, have distinct characteristics, and contribute to psoriatic pathogenesis.

Highlights

Psoriasis (PS) is a chronic, inflammatory, and immune-mediated skin disease, characterized by raised, red scaly plaques [1]
CAT uses no information of splicing signals or genome annotation for circRNA detection but uses genome annotation to classify circRNAs into the categories of canonical circRNAs with two back-fusion (BF) points at intronexon boundaries, complete i-circRNAs with both BF points not residing at intron-exon boundaries, and partial i-circRNAs with one BF point from an intron-exon boundary [46]
When applied to paired-end RNA-seq data, it detects a circRNA if one end of a paired-end read is mapped to the genome in an orientation-reversed splitting form; the splitting points define the back-splicing or BF point of the circRNA (Figure 1a)

Summary

Introduction

Psoriasis (PS) is a chronic, inflammatory, and immune-mediated skin disease, characterized by raised, red scaly plaques [1]. Besides the long-lasting and high recurrence rate, PS may increase the risk of stroke [3], myocardial infarction [4], type 2 diabetes [5], metabolic syndrome [6,7], and cancer [8,9]. Studies in the past decades have identified many genetic risk factors [10,11] and aberrant expression of many transcripts including non-coding RNAs such as microRNAs (miRNAs) [12,13,14,15] and long non-coding RNAs (lncRNAs) [16]. MiR-21 contributes to T-cell derived psoriatic skin inflammation [17], and miR-31 overexpression enhances the production of inflammatory cytokines and chemokines [18]. Many lncRNAs function in PS, e.g., PRINS [19,20], lnc-IL7R [21], and LincR-Ccr AS [22]

Methods

Results

Discussion

Conclusion