生物
癌变
选择性拼接
基因
内含子
癌症研究
遗传学
RNA剪接
免疫系统
外显子
核糖核酸
细胞生物学
计算生物学
作者
Quanyou Wu,Yuan Zhang,Haiyin An,Wei Sun,Ruozheng Wang,Meng Li,Kaitai Zhang
出处
期刊:Oncogene
[Springer Nature]
日期:2021-06-02
卷期号:40 (24): 4184-4197
被引量:8
标识
DOI:10.1038/s41388-021-01849-8
摘要
Aberrant alternative splicing events (AASEs) are key biological processes for tumorigenesis and the rationale for designing splice-switching oligonucleotides (SSOs). However, the landscape of AASEs in esophageal squamous cell carcinoma (ESCC) remains unclear, which undermines the development of SSOs for ESCC. Here, we profiled AASEs based on 125 pairs of RNA-seq libraries. We identified 14,710 AASEs in ESCC, most of which (92.67%) affected coding genes. The first exon of was frequently changed in ESCC. We constructed a regulatory network where 74 RNA-binding proteins regulated 2142 AASEs. This network was enriched in apoptotic pathways and various adhesion/junction-related processes. Somatic mutations in ESCC regulating ASEs were mainly through trans-regulatory mode and were enriched in intron regions. Isoform switches of apoptotic genes and binding genes both tended to induce noncoding transcripts and domain loss, disrupting the apoptotic and Hippo signaling pathways. All ESCC samples were grouped into three clusters with different AASEs patterns and the second cluster was identified as cold tumor, with a low abundance of immune cells, activated immune pathways, and immunomodulators. Our work comprehensively profiled the landscape of AASEs in ESCC, revealed novel AASEs related to tumorigenesis and immune microenvironment, and suggested promising directions for designing SSOs for ESCC.
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