Profiles of gene expression and alternative splicing in K562 cells exposed to 2 mM sodium valproate for 12 hours assessed using exon array

To investigate the effect of valproate (VPA) treatment on K562 cell line, the growth and survival of the K562 cell line were investigated using the Annexin V/PI dual staining method, and global profiles of gene expression and alternative splicing in K562 cells were assessed using exon microarray. A significant increase in cell apoptosis was observed in valproate exposed K562 cells using flow cytometry. A total of 628 transcripts were identified as being significantly differentially expressed. The number of genes demonstrating increased expression levels was greater than the number of genes demonstrating decreased expression levels (445 genes vs. 183 genes, respectively). The significant enrichment analysis of GO terms for the differentially expressed genes revealed that these genes are involved in many important biological processes such as apoptosis. Six of observed differentially expressed genes that might be involved in apoptosis were selected to undergo qRT-PCR validation. In total, 198 candidates of alternative splicing variants were identified. Among them, three alternative splicing events were selected for validation, and CBLC and TBX1 were confirmed as alternative splicing by semi-nested PCR. In conclusion, valproate exposure facilitated cell apoptosis, altered mRNA expression and alternative splicing events in the K562 cell line.