%0 Journal Article
%T The MYC 3¡ä Wnt-Responsive Element Drives Oncogenic MYC Expression in Human Colorectal Cancer Cells
%A Gregory S. Yochum
%A Melanie A. Eshelman
%A Sherri A. Rennoll
%A Wesley M. Raup-Konsavage
%A Yuka Imamura Kawasawa
%J Archive of "Cancers".
%D 2016
%R 10.3390/cancers8050052
%X Mutations in components of the Wnt/¦Â-catenin signaling pathway drive colorectal cancer (CRC) by deregulating expression of downstream target genes including the c-MYC proto-oncogene (MYC). The critical regulatory DNA enhancer elements that control oncogenic MYC expression in CRC have yet to be fully elucidated. In previous reports, we correlated T-cell factor (TCF) and ¦Â-catenin binding to the MYC 3¡ä Wnt responsive DNA element (MYC 3¡ä WRE) with MYC expression in HCT116 cells. Here we used CRISPR/Cas9 to determine whether this element is a critical driver of MYC. We isolated a clonal population of cells that contained a deletion of a single TCF binding element (TBE) within the MYC 3¡ä WRE. This deletion reduced TCF/¦Â-catenin binding to this regulatory element and decreased MYC expression. Using RNA-Seq analysis, we found altered expression of genes that regulate metabolic processes, many of which are known MYC target genes. We found that 3¡ä WRE-Mut cells displayed a reduced proliferative capacity, diminished clonogenic growth, and a decreased potential to form tumors in vivo. These findings indicate that the MYC 3¡ä WRE is a critical driver of oncogenic MYC expression and suggest that this element may serve as a therapeutic target for CRC
%K MYC
%K Wnt-responsive element
%K ¦Â-catenin
%K colorectal cancer
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880869/