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 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 microarrays. 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 the genes observed to be differentially expressed 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 to be alternatively spliced by semi-nested PCR. In conclusion,             valproate exposure facilitated cell apoptosis, altered mRNA expression and alternative             splicing events in the K562 cell line.
Department of Hematology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China.
Xiang-Zhong
XZ
Zhang
Ai-Hua
AH
Yin
Xiao-Yu
XY
Zhu
Qian
Q
Ding
Chun-Huai
CH
Wang
Yun-Xian
YX
Chen
D017398:Alternative Splicing / Q000187:drug effects*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005091:Exons; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D053263:Gene Regulatory Networks / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014635:Valproic Acid / Q000494:pharmacology*
D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D012333:RNA, Messenger; D014635:Valproic Acid