Using an exon microarray to identify a global profile of gene expression and alternative splicing in K562 cells exposed to sodium valproate

To investigate the effect of valproate treatment on the K562 cell line,a model for chronic myelogenous leukaemia, the growth and survival of the K562cell line were investigated using the Annexin-V/PI dual staining method, and globalprofiles of gene expression and alternative splicing in K562 cells were assessedusing exon microarrays. A significant increase in cell apoptosis was observedin valproate-exposed K562 cells using flow cytometry. A total of 628 transcriptswere identified as being significantly differentially expressed. The number ofgenes demonstrating increased expression levels was greater than the number ofgenes demonstrating decreased expression levels (445 genes vs. 183 genes, respectively).The significant enrichment analysis of GO terms for the differentially expressedgenes revealed that these genes are involved in many important biological processessuch as apoptosis. Six of the genes observed to be differentially expressed thatmight be involved in apoptosis were selected to undergo qRT-PCR validation. Intotal, 198 candidates of alternative splicing variants were identified. Amongthem, three alternative splicing events were selected for validation, and CBLCand TBX1 were confirmed to be alternatively spliced by semi-nested PCR. In conclusion,valproate exposure facilitated cell apoptosis, altered mRNA expression and alternativesplicing events in the K562 cell line.