The role of FOXM1 and Kaiso in non-small-cell lung carcinoma (NSCLC)

Abstract

FoxM1 and Kaiso are two important oncogenes in non-small cell lung carcinomas, however few studies demonstrate the direct regulatory relationship between FOXM1 and ZBTB33. We have performed CHIPseq of FOXM1, H3K27ac and H3K27me3 in PTC02 (a local non-small lung cancer cells) and RNAseq between PCT02 and normal control tissues. FOXM1 genome-wide ChIP-seq data showed that ZBTB33 (Kaiso) binding motif was significantly enriched on FOXM1 binding sites in PTC02, GM12878 and ECC1. The regions with both FOXM1 binding and Kaiso motif, which were defined as F&K regions, had higher level of FOXM1 binding tags and higher ratio of sites occupied by FOXM1, compared to the regions merely with FOXM1 binding sites (defined as F region) or the Kaiso motif (defined as K region). The F&K regions were also highly bound by the Kaiso protein across five cell lines GM12878, A549, SKnsh, Hepg2, K562 with over 90% of sites occupied by Kaiso. Interestingly, higher level of H3K27ac and lower level of H3K27me3 appeared on the F&K region than F or K regions. The genes associated with F&K regions were significantly upregulated in PCT02 and 60 paired lung cancer tissues. Functional enrichment analysis showed that these F&K associated genes were highly enriched on the UBC (ubiquitin C) interaction partners. In summary, this study suggests that the FOXM1 and Kaiso might work together to upregulate ubiquitin C related genes for promoting non-small cell lung cancer. Further studies will investigate causal the relation between FOXM1 and Kaiso by knockdown of FOXM1 or Kaiso.