FOXD3 suppresses tumor-initiating features in lung cancer via transcriptional repression of WDR5 and SET

In this study, we demonstrated that FOXD3, acting as a repressor in the expansion of lung cancer TICs, was negatively correlated with histological grades and metastasis in lung cancer, and provided evidence that FOXD3 repressed the TIC expansion, cell invasion and drug resistance in vivo and in vitro. Global genomic RNA-Seq and Chip-seq analyses identified WDR5 and SET as the direct targets of FOXD3 in lung cancer. Inhibition of WDR5 and SET could partially rescue TIC abundance, cell invasion, osteogenesis, and gene expression signature upon depletion of FOXD3. Clinically, we revealed that FOXD3 was negatively correlated with WDR5 and SET expression, CSC abundance, and prognosis of lung cancer. mRNA profiles of wild type (WT) and siFOXD3 of A549 cells were generated by deep sequencing, using Illumina Genome Analyzer.