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Carcinogenesis. 2019 Jan 30. doi: 10.1093/carcin/bgz010. [Epub ahead of print]

O-GlcNAcylation of YY1 stimulates tumorigenesis in colorectal cancer cells by targeting SLC22A15 and AANAT.

Author information

1
Department of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
2
Department of General Surgery, Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
3
Department of Clinical Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Abstract

Emerging studies have revealed that O-GlcNAcylation plays pivotal roles in the tumorigenesis of colorectal cancers. However, the underlying mechanism still remains largely unknown. Here, we demonstrated that YY1 was O-GlcNAcylated by OGT and O-GlcNAcylation of YY1 could increase the protein expression by enhancing its stability. O-GlcNAcylation facilitated transformative phenotypes of CRC cell in a YY1-dependent manner. Also, O-GlcNAcylation stimulates YY1-dependent transcriptional activity. Besides, we also identified the oncoproteins, SLC22A15 and AANAT, which were regulated by YY1 directly, are responsible for the YY1 stimulated tumorigenesis. Furthermore, we identified the main putative O-GlcNAc site of YY1 at Thr236, and mutating of this site decreased the pro-tumorigenic capacities of YY1. We concluded that O-GlcNAcylation of YY1 stimulates tumorigenesis in CRC cells by targeting SLC22A15 and AANAT, suggesting that YY1 O-GlcNAcylation might be a potential effective therapeutic target for treating CRC.

PMID:
30715269
DOI:
10.1093/carcin/bgz010

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