IDENTIFICATION OF POST-TRANSCRIPTIONAL REGULATORS OF MYC IN COLORECTAL CANCER

Abstract

Elevated MYC transcript levels in colorectal cancer (CRC) patients highlight the importance of MYC regulation in CRC development. In my thesis, I explored alternative strategies that could modulate MYC expression and identified two post-transcriptional regulators. Firstly, I identified LARP1 as an RBP which associates with the MYC 3′UTR, thereby positively regulating MYC expression. In addition, I discovered that MYC is a positive regulator of LARP1 at the transcriptional level. Secondly, I identified miR-138-5p as a negative regulator of MYC expression via its targeting of the MYC coding sequence (CDS). Overexpression of miR-138-5p decreases MYC expression and inhibits CRC tumorigenesis in vitro, while the inhibition of miR-138-5p reverses these effects. The elucidation of the mechanistic roles of these two post-transcriptional regulators of MYC provides a better understanding of the molecular basis of MYC dysregulation in CRC and may serve as alternatives for treatment of MYC-driven CRC and possibly other MYC-driven cancers.