Department of Radiology, The People's Hospital of China Medical University & The People's Hospital of Liaoning Province, No. 33, Wenyi Road, Shenhe District, Shenyang, 110016, China.
Department of Gastroenterology, Shengjing Hospital of China Medical University, Tiexi District, 39 Huaxiang Road, Shenyang, 110022, China.
Biomed Eng Online. 2021 Nov 27;20(1):121. doi: 10.1186/s12938-021-00959-4.
Although numerous risk loci for ulcerative colitis (UC) have been identified in the human genome, the pathogenesis of UC remains unclear. Recently, multiple transcriptomic analyses have shown that aberrant gene expression in the colon tissues of UC patients is associated with disease progression. A pioneering study also demonstrated that altered post-transcriptional regulation is involved in the progression of UC. Here, we provide a genome-wide analysis of alternative splicing (AS) signatures in UC patients. We analyzed three datasets containing 74 tissue samples from UC patients and identified over 2000 significant AS events.
Skipped exon and alternative first exon were the two most significantly altered AS events in UC patients. The immune response-related pathways were remarkably enriched in the UC-related AS events. Genes with significant AS events were more likely to be dysregulated at the expression level.
We present a genomic landscape of AS events in UC patients based on a combined analysis of two cohorts. Our results indicate that dysregulation of AS may have a pivotal role in determining the pathogenesis of UC. In addition, our study uncovers genes with potential therapeutic implications for UC treatment.
虽然人类基因组中已经确定了许多溃疡性结肠炎 (UC) 的风险基因座，但 UC 的发病机制仍不清楚。最近，多项转录组分析表明，UC 患者结肠组织中的异常基因表达与疾病进展有关。一项开创性的研究还表明，转录后调控的改变与 UC 的进展有关。在这里，我们对 UC 患者的可变剪接 (AS) 特征进行了全基因组分析。我们分析了包含 74 个 UC 患者组织样本的三个数据集，鉴定出了 2000 多个显著的 AS 事件。
UC 患者中最显著的两种可变剪接事件是外显子跳跃和可变外显子 1。与 UC 相关的 AS 事件显著富集于免疫反应相关通路。具有显著 AS 事件的基因更有可能在表达水平上失调。
我们基于对两个队列的联合分析，呈现了 UC 患者的 AS 事件的基因组图谱。我们的结果表明，AS 的失调可能在决定 UC 的发病机制中起着关键作用。此外，我们的研究揭示了一些具有 UC 治疗潜在治疗意义的基因。
