RNA sequencing analysis of A549 cells using siRNAs of control and oncogene DEK
An oncogenic protein, DEK, is highly expressed in growing cells including cancers. Overexpression of DEK is associated with poor prognosis in a variety of cancers. However, the molecular mechanisms by which DEK promotes cancer development and malignant transformation remain unclear. Previous studies have shown that DEK interacts with transcription factors such as AP-2a and C/EBPalpha and enhances their transcriptional activity. We hypothesized that DEK promotes cancer cell phenotypes by regulating transcription factors. To test this hypothesis, we analyzed the interaction between DEK and transcription factors. We found that DEK binds to the basic regions within the basic leucine zipper (bZIP)- and basic helix-loop-helix leucine zipper (bHLH-Zip)-transcription factors. Interestingly, we showed that DEK enhances the DNA binding capacity of two bZIP transcription factors, C/EBPalpha and ATF3, in vitro without being a component of the transcription factor-DNA complex. To address the biological significance of the interaction between DEK and transcription factors, we examined the global transcriptome changes upon DEK knockdown in lung adenocarcinoma A549 cells. We found that diverse genes regulating cell growth and amino acid metabolism, which are potentially regulated by c-JUN (a subunit of the bZIP transcription factor AP1) and c-Myc (a bHLH-ZIP transcription factor), were decreased by DEK knockdown. Consistent with these transcriptome changes, cell growth, colony formation, and cell migration abilities of A549 cells were decreased upon DEK KD. Our results suggest that DEK promotes cancer cell malignancy by regulating the functions of bZIP and bHLH-ZIP transcription factors. Overall design: A549 cells were transfected with siRNAs named siNC (Negative Control), siDEK1, and siDEK2. Four days after transfection, cells were examined with RNA sequencing analysis, identifying differentially expressed genes caused by DEK knockdown in A549.