鉴定银屑病和特应性皮炎中的环状 RNA 转录组,揭示疾病特异性表达谱。

Characterization of circular RNA transcriptomes in psoriasis and atopic dermatitis reveals disease-specific expression profiles.

机构信息

Department of Molecular Biology and Genetics (MBG), Aarhus University, Aarhus C, Denmark.

Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus C, Denmark.

出版信息

Exp Dermatol. 2021 Aug;30(8):1187-1196. doi: 10.1111/exd.14227. Epub 2020 Nov 16.

Abstract

Atopic dermatitis (AD) and psoriasis are two common chronic inflammatory skin diseases that are associated with various comorbidities. Circular RNA (circRNA) constitutes a major class of non-coding RNAs that have been implicated in many human diseases, although their potential involvement in inflammatory skin diseases remains elusive. Here, we compare and contrast the circRNA expression landscapes in paired lesional and non-lesional skin from psoriasis and AD patients relative to skin from unaffected individuals using high-depth RNA-seq data. CircRNAs and their cognate linear transcripts were quantified using the circRNA detection algorithm, CIRI2, and in situ hybridization and Sanger sequencing was used for validation purposes. We identified 39,286 circRNAs among all samples and found that psoriasis and AD lesional skin could be distinguished from non-lesional and healthy skin based on circRNA expression landscapes. In general, circRNAs were less abundant in lesional relative to non-lesional and healthy skin. Differential expression analyses revealed many significantly downregulated circRNAs, mainly in psoriasis lesional skin, and a strong correlation between psoriasis and AD-related circRNA expression changes was observed. Two individual circRNAs, ciRS-7 (also known as CDR1as) and circZRANB1, were specifically dysregulated in psoriasis and show promise as biomarkers for discriminating AD from psoriasis. In conclusion, the circRNA transcriptomes of psoriasis and AD share expression features, including a global downregulation relative to healthy skin, but this is most pronounced in psoriasis, and only psoriasis is characterized by several circRNAs being dysregulated independently of their cognate linear transcripts. Finally, specific circRNAs could potentially be used to distinguish AD from psoriasis.

摘要

特应性皮炎(AD)和银屑病是两种常见的慢性炎症性皮肤病,与多种合并症相关。环状 RNA(circRNA)是一类主要的非编码 RNA,已被证实与许多人类疾病有关,尽管它们在炎症性皮肤病中的潜在作用仍不明确。在这里,我们使用深度 RNA-seq 数据,比较和对比了来自银屑病和 AD 患者皮损和非皮损皮肤与正常皮肤之间的 circRNA 表达图谱。使用 circRNA 检测算法 CIRI2 定量 circRNA 和其同源线性转录本,并进行原位杂交和 Sanger 测序验证。我们在所有样本中鉴定了 39286 个 circRNA,发现银屑病和 AD 皮损皮肤可以基于 circRNA 表达图谱与非皮损和正常皮肤区分开来。一般来说,circRNA 在皮损中比非皮损和正常皮肤中更为丰富。差异表达分析显示,许多显著下调的 circRNA 主要在银屑病皮损中,并且观察到银屑病和 AD 相关 circRNA 表达变化之间存在很强的相关性。两个个体 circRNA,ciRS-7(也称为 CDR1as)和 circZRANB1,在银屑病中特异性失调,并有望作为区分 AD 与银屑病的生物标志物。总之,银屑病和 AD 的 circRNA 转录组具有表达特征,包括与正常皮肤相比的全局下调,但在银屑病中最为明显,只有银屑病的几个 circRNA 失调与它们的同源线性转录本无关。最后,特定的 circRNA 可能可用于区分 AD 与银屑病。

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