Department of Radiology, The People's Hospital of China Medical University and 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, 39 Huaxiang Road, Tiexi District, Shenyang, 110022, China.
BMC Gastroenterol. 2021 Nov 8;21(1):420. doi: 10.1186/s12876-021-02001-2.
Although hundreds of risk loci for Crohn's disease (CD) have been identified, the underlying pathogenesis of CD remains unclear. Recently, evidence has shown that aberrant gene expression in colon tissues of CD patients is associated with the progression of CD. We reasoned that post-transcriptional regulation, especially alternative splicing (AS), may also play important roles in the pathogenesis of CD.
We re-analyzed public mRNA-seq data from the NCBI GEO dataset (GSE66207) and identified approximately 3000 unique AS events in CD patients compared to healthy controls.
"Lysine degradation" and "Sphingolipid metabolism" were the two most enriched AS events in CD patients. In a validation study, we also sequenced eight subjects and demonstrated that key genes that were previously linked to CD, such as IRF1 and STAT3, also had significant AS events in CD.
Our study provided a landscape of AS events in CD, especially as the first study focused on a Chinese cohort. Our data suggest that dysregulation of AS may be a new mechanism that contributes to the pathogenesis of CD.
尽管已经发现了数百个克罗恩病 (CD) 的风险基因座，但 CD 的潜在发病机制仍不清楚。最近的证据表明，CD 患者结肠组织中的异常基因表达与 CD 的进展有关。我们推测，转录后调控，特别是选择性剪接 (AS)，也可能在 CD 的发病机制中发挥重要作用。
我们重新分析了来自 NCBI GEO 数据集（GSE66207）的公共 mRNA-seq 数据，与健康对照组相比，在 CD 患者中鉴定出大约 3000 个独特的 AS 事件。
“赖氨酸降解”和“鞘脂代谢”是 CD 患者中最丰富的两个 AS 事件。在一项验证研究中，我们还对 8 名受试者进行了测序，结果表明，先前与 CD 相关的关键基因，如 IRF1 和 STAT3，在 CD 中也存在显著的 AS 事件。
我们的研究提供了 CD 中 AS 事件的全景图，特别是作为第一项专注于中国队列的研究。我们的数据表明，AS 的失调可能是导致 CD 发病机制的新机制。
