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.

• Authors: Nan Wu, Mingzuo Jiang, Yuying Han, Haiming Liu, Yi Chu, Hao Liu, Jiayi Cao, Qiuqiu Hou, Yu Zhao, Bing Xu, Xin Xie
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 23 Issue 2 Pg. 1354-1362 (02 2019) ISSN: 1582-4934 [Electronic] England
• PMID: 30484950 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• Biomarkers, Tumor
• N-Acetylglucosaminyltransferases
• MTOR protein, human
• AKT1 protein, human
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases
• Ddx5 protein, human
• DEAD-box RNA Helicases

Topics

• Animals
• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Cell Movement
• Cell Proliferation
• Colorectal Neoplasms (genetics, metabolism, pathology)
• DEAD-box RNA Helicases (chemistry, genetics, metabolism)
• Disease Progression
• Gene Expression Regulation, Neoplastic
• Glycosylation
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• N-Acetylglucosaminyltransferases (metabolism)
• Protein Processing, Post-Translational
• Protein Stability
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• TOR Serine-Threonine Kinases (genetics, metabolism)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays