O‐GlcNAcylation promotes colorectal cancer progression by regulating protein stability and potential catcinogenic function of DDX5

The RNA helicase p68 (DDX5), a key player in RNA metabolism, belongs to the DEAD box family and is involved in the development of colorectal cancer. Here, we found both DDX5 and O‐GlcNAcylation are up‐regulated in colorectal cancer. In addition, DDX5 protein level is significantly positively correlated with the expression of O‐GlcNAcylation. Although it was known DDX5 protein could be regulated by post‐translational modification (PTM), how O‐GlcNAcylation modification regulated of DDX5 remains unclear. Here we show that DDX5 interacts directly with OGT in the SW480 cell line, which is the only known enzyme that catalyses O‐GlcNAcylation in humans. Meanwhile, O‐GlcNAcylation could promote DDX5 protein stability. The OGT‐DDX5 axis affects colorectal cancer progression mainly by regulating activation of the AKT/mTOR signalling pathway. Taken together, these results indicated that OGT‐mediated O‐GlcNAcylation stabilizes DDX5, promoting activation of the AKT/mTOR signalling pathway, thus accelerating colorectal cancer progression. This study not only reveals the novel functional of O‐GlcNAcylation in regulating DDX5, but also reveals the carcinogenic effect of the OGT‐DDX5 axis in colorectal cancer.