DEK modulates both expression and alternative splicing of cancer­related genes.

DEK is known to be a potential proto­oncogene and is highly expressed in gastric cancer (GC); thus, DEK is considered to contribute to the malignant progression of GC. DEK is an RNA­binding protein involved in transcription, DNA repair, and selection of splicing sites during mRNA processing; however, its precise function remains elusive due to the lack of clarification of the overall profiles of gene transcription and post­transcriptional splicing that are regulated by DEK. We performed our original whole­genomic RNA­Seq data to analyze the global transcription and alternative splicing profiles in a human GC cell line by comparing DEK siRNA­treated and control conditions, dissecting both differential gene expression and potential alternative splicing events regulated by DEK. The siRNA­mediated knockdown of DEK in a GC cell line led to significant changes in gene expression of multiple cancer­related genes including both oncogenes and tumor suppressors. Moreover, it was revealed that DEK regulated a number of alternative splicing in genes which were significantly enriched in various cancer­related pathways including apoptosis and cell cycle processes. This study clarified for the first time that DEK has a regulatory effect on the alternative splicing, as well as on the expression, of numerous cancer­related genes, which is consistent with the role of DEK as a possible oncogene. Our results further expand the importance and feasibility of DEK as a clinical therapeutic target for human malignancies including GC.