Kõks Sulev, Keermann Maris, Reimann Ene, Prans Ele, Abram Kristi, Silm Helgi, Kõks Gea, Kingo Kulli
Department of Pathophysiology, Centre of Translational Medicine, University of Tartu, Tartu, Estonia; Department of Reproductive Biology, Estonian University of Life Sciences, Tartu, Estonia.
Department of Dermatology, University of Tartu, Tartu, Estonia; Department of Dermatology, Tartu University Hospital, Tartu, Estonia.
Front Med (Lausanne). 2016 Oct 7;3:46. doi: 10.3389/fmed.2016.00046. eCollection 2016.
Several studies have been published that investigated potential links between transcriptome changes and psoriasis using microarrays and RNA-seq technologies, but no previous study has analyzed expression profile of alternatively spliced transcripts in psoriasis.
Identification of potential alternatively spliced RNA isoforms with disease-specific expression profile.
Using our published RNA sequencing data from lesional psoriatic (LP), non-lesional psoriatic (NLP), and normal control skin (C), we analyzed the differential expression of RNA splicing variants. LP sample was compared with NLP, as was LP with C and NLP with C.
Transcript-based annotation analyzed 173,446 transcripts (RNA isoforms), and around 9,000 transcripts were identified as differentially expressed between study groups. Several previously undescribed RNA variants were found. For instance, transcript ETV3_3 (ENST00000326786) was significantly downregulated in LP and NLP skin. ETV3 is a transcriptional repressor that contributes to the downstream anti-inflammatory effects of IL-10. We also identified diseases-specific transcripts (S100A7A, IL36RN_4, and IL36G_3) of genes already recognized to be involved in inflammation and immune response.
Psoriasis is characterized by significant differences in the expression of RNA alternative isoforms. Description of these new isoforms improves our knowledge about this complex disease.
已有多项研究利用微阵列和RNA测序技术探究转录组变化与银屑病之间的潜在联系,但此前尚无研究分析银屑病中可变剪接转录本的表达谱。
鉴定具有疾病特异性表达谱的潜在可变剪接RNA异构体。
利用我们已发表的来自银屑病皮损(LP)、非皮损银屑病(NLP)和正常对照皮肤(C)的RNA测序数据,分析RNA剪接变体的差异表达。将LP样本与NLP样本进行比较,LP与C以及NLP与C也进行比较。
基于转录本的注释分析了173,446个转录本(RNA异构体),研究组之间约9,000个转录本被鉴定为差异表达。发现了几种先前未描述的RNA变体。例如,转录本ETV3_3(ENST00000326786)在LP和NLP皮肤中显著下调。ETV3是一种转录抑制因子,有助于IL-10的下游抗炎作用。我们还鉴定了已被认为参与炎症和免疫反应的基因的疾病特异性转录本(S100A7A、IL36RN_4和IL36G_3)。
银屑病的特征是RNA可变异构体的表达存在显著差异。对这些新异构体的描述增进了我们对这种复杂疾病的了解。