1. Transcriptome-wide analysis of alternative RNA splicing events in Epstein-Barr virus-associated gastric carcinomas.
- Author
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Armero VES, Tremblay MP, Allaire A, Boudreault S, Martenon-Brodeur C, Duval C, Durand M, Lapointe E, Thibault P, Tremblay-Létourneau M, Perreault JP, Scott MS, and Bisaillon M
- Subjects
- Adenocarcinoma genetics, Adenocarcinoma pathology, Adenocarcinoma virology, Epstein-Barr Virus Nuclear Antigens genetics, Epstein-Barr Virus Nuclear Antigens metabolism, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, HEK293 Cells, Humans, Protein Binding, RNA Splicing Factors metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, RNA, Small Interfering metabolism, Reproducibility of Results, Stomach Neoplasms pathology, Survival Analysis, Alternative Splicing genetics, Epstein-Barr Virus Infections genetics, Gene Expression Profiling, Herpesvirus 4, Human physiology, RNA, Neoplasm genetics, Stomach Neoplasms genetics, Stomach Neoplasms virology
- Abstract
Multiple human diseases including cancer have been associated with a dysregulation in RNA splicing patterns. In the current study, modifications to the global RNA splicing landscape of cellular genes were investigated in the context of Epstein-Barr virus-associated gastric cancer. Global alterations to the RNA splicing landscape of cellular genes was examined in a large-scale screen from 295 primary gastric adenocarcinomas using high-throughput RNA sequencing data. RT-PCR analysis, mass spectrometry, and co-immunoprecipitation studies were also used to experimentally validate and investigate the differential alternative splicing (AS) events that were observed through RNA-seq studies. Our study identifies alterations in the AS patterns of approximately 900 genes such as tumor suppressor genes, transcription factors, splicing factors, and kinases. These findings allowed the identification of unique gene signatures for which AS is misregulated in both Epstein-Barr virus-associated gastric cancer and EBV-negative gastric cancer. Moreover, we show that the expression of Epstein-Barr nuclear antigen 1 (EBNA1) leads to modifications in the AS profile of cellular genes and that the EBNA1 protein interacts with cellular splicing factors. These findings provide insights into the molecular differences between various types of gastric cancer and suggest a role for the EBNA1 protein in the dysregulation of cellular AS.
- Published
- 2017
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