Alterations of RNA splicing patterns in esophagus squamous cell carcinoma

Cell & Bioscience

Zepeng Du¹  Enmin Li²  Qiaoxi Xia²  Jiyu Ding²  Wei Liu²  Ling Lin²  Wenjing Bai²  Yinwei Cheng²  Bingli Wu²  Liyan Xu³  Zhidong Tang⁴  Chunquan Li⁴  Qiuyu Wang⁴  Chao Song⁴ 

[1] Department of Pathology, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, 515041, Shantou, China;Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, 515041, Shantou, China;Department of Biochemistry and Molecular Biology, Shantou University Medical College, 515041, Shantou, China;Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, 515041, Shantou, China;Institute of Oncologic Pathology, Shantou University Medical College, 515041, Shantou, China;School of Medical Informatics, Harbin Medical University, Daqing Campus, 163319, Daqing, China;

关键词: Alternative splicing;    MISO;    Esophagus squamous cell carcinoma;   

DOI  :  10.1186/s13578-021-00546-z

来源: Springer

【 摘 要 】

Alternative splicing (AS) is an important biological process for regulating the expression of various isoforms from a single gene and thus to promote proteome diversity. In this study, RNA-seq data from 15 pairs of matched esophageal squamous cell carcinoma (ESCC) and normal tissue samples as well as two cell lines were analyzed. AS events with significant differences were identified between ESCC and matched normal tissues, which were re-annotated to find protein coding genes or non-coding RNAs. A total of 45,439 AS events were found. Of these, 6019 (13.25%) significant differentially AS events were identified. Exon skipping (SE) events occupied the largest proportion of abnormal splicing events. Fifteen differential splicing events with the same trends of ΔΨ values in ESCC tissues, as well in the two cell lines were found. Four pathways and 20 biological processes related to pro-metastasis cell junction and migration were significantly enriched for the differentially spliced genes. The upregulated splicing factor SF3B4, which regulates 92 gene splicing events, could be a potential prognostic factor of ESCC. Differentially spliced genes, including HNRNPC, VCL, ZNF207, KIAA1217, TPM1 and CALD1 are shown with a sashimi plot. These results suggest that cell junction- and migration-related biological processes are influenced by AS abnormalities, and aberrant splicing events can be affected by splicing factor expression changes. The involved splicing factor SF3B4 was found to be a survival-related gene in ESCC and is presumed to regulate AS in multiple cancers. In summary, we identified significant differentially expressed AS events which may be related to the development of ESCC.

【 授权许可】

CC BY