MRGBP promotes colorectal cancer metastasis via DKK1/Wnt/β-catenin and NF-kB/p65 pathways mediated EMT

Abstract

MRG domain binding protein (MRGBP) has been proposed to participate in the development of multiple tumors. However, the role of MRGBP in colorectal cancer (CRC) still remains largely unknown. Here, we found that MRGBP expression is significantly elevated in CRC, and that higher MRGBP expression correlates with poorer survival in CRC patients. Experiments in vivo and in vitro indicated that MRGBP promotes CRC cells proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) and xenograft tumor growth. Mechanically, for one thing, we discovered that MRGBP suppresses DKK1 expression, thus further activating the Wnt/β-catenin pathway in CRC cells. For another, MRGBP also enhances acetylation of NF-kB/p65 pathway. Treatment with Wnt/β-catenin and NF-kB pathways inhibitors further confirmed the mediation of these two pathways in MRGBP-promoted CRC cell processes. In conclusion, these findings together suggest that MRGBP promotes CRC progression via DKK1/Wnt/β-catenin and NF-kB/p65 pathways mediated EMT, identifying MRGBP as a promising prognostic and therapeutic target for CRC.