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


ABSTRACT: 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.

SUBMITTER: Wu N 

PROVIDER: S-EPMC6349181 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Wu Nan N   Jiang Mingzuo M   Han Yuying Y   Liu Haiming H   Chu Yi Y   Liu Hao H   Cao Jiayi J   Hou Qiuqiu Q   Zhao Yu Y   Xu Bing B   Xie Xin X  

Journal of cellular and molecular medicine 20181128 2


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 u  ...[more]

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