The c-MYC-WDR43 signalling axis promotes chemoresistance and growth in colorectal cancer by inhibiting p53 activity

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Oxaliplatin chemoresistance is a major challenge in the clinical treatment of CRC. Through bioinformatics analysis, we identified WDR43 as a critical potential oncogenic factor in CRC pathogenesis. Clinically, WDR43 is highly expressed in CRC, and WDR43 overexpression is associated with poor prognosis in CRC patients. WDR43 knockdown significantly inhibits cell growth by arresting the cell cycle and enhances the effect of oxaliplatin chemotherapy capacities in vitro and in vivo. Mechanistically, upon oxaliplatin stimulation, c-MYC promotes the transcriptional regulation and expression of WDR43. WDR43 enhances the ubiquitination of p53 by MDM2 by binding RPL11, thereby reducing the stability of the p53 protein, which further induces the proliferation and chemoresistance of CRC cells. Thus, WDR43 may not only mark CRC progression but also be a potential therapeutic target of chemoresistance in CRC. WDR43 were knocked down in HCT116 cells, and the differences in gene expression were compared with shNC, respectively, using RNAseq.