MYC binding to the E-box in the 5-UTR of Nle1 predisposes mice to intestinal tumors

Nle1 encodes a WD40 repeats-containing protein highly conserved in eukaryotes and involved in Notch signaling pathway. Previous studies have shown that inhibition/loss-of-function of NLE1 alleviates development of malignant tumors, while it remains largely unclear the exact roles and underlying mechanism of NLE1 involved in this process. We have learned from our earlier research that the E-box in the 5-UTR of Nle1 was probably a binding target of MYC, a well-known oncogene contributing to the intestinal tumorigenesis, which thus integrates NLE1 into the MYC sigalling cascade. In this context, we silence the E-box in mice by shuffling its sequence to examine the resistance to intestinal tumorigenesis induced by the APCmin mutation. These results will expand our understanding of the regulatory effect of MYC on expression of Nle1 through binding to its E-box upstream the transcription starting site.