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Chromatin-associated OGT promotes hepatocellular carcinoma malignancy via activating ZNF263 [ChIP-seq]

ABSTRACT: The reversible and dynamic O-GlcNAcylation regulates vast networks of highly coordinated cellular and nuclear processes. Despite the dysregulation of the sole enzyme O-GlcNAc transferase (OGT), is showed to associated with the progression of hepatocellular carcinoma (HCC), the mechanisms by which OGT controls the cis-regulatory elements in the genome and achieves transcriptional functions remain unclear. Here, we demonstrate that the elevated OGT increases HCC proliferation and metastasis by orchestrating the transcription of numerous malignant regulators in vitro and in vivo. Diverse transcriptional regulators are recruited by OGT in HCC cells with progressive malignancy, which shapes the genome-wide OGT chromatin cis-elements occupation. Further, an unrecognized cooperation between ZNF263 and OGT is crucial for activating downstream transcriptomics. We reveal that the O-GlcNAcylation site Ser662 is responsible for ZNF263 chromatin association at candidate gene promoters and OGT facilitated HCC the malignant phenotypes. Our data establish the importance of aberrant OGT and ZNF263 O-GlcNAcylation in HCC malignant progression, and represents the pursuit of OGT as a target for HCC therapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE222280 | GEO | 2023/01/09

REPOSITORIES: GEO

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Chromatin-associated OGT promotes hepatocellular carcinoma malignancy via activating ZNF263 [RNA-seq]

Project description:The reversible and dynamic O-GlcNAcylation regulates vast networks of highly coordinated cellular and nuclear processes. Despite the dysregulation of the sole enzyme O-GlcNAc transferase (OGT), is showed to associated with the progression of hepatocellular carcinoma (HCC), the mechanisms by which OGT controls the cis-regulatory elements in the genome and achieves transcriptional functions remain unclear. Here, we demonstrate that the elevated OGT increases HCC proliferation and metastasis by orchestrating the transcription of numerous malignant regulators in vitro and in vivo. Diverse transcriptional regulators are recruited by OGT in HCC cells with progressive malignancy, which shapes the genome-wide OGT chromatin cis-elements occupation. Further, an unrecognized cooperation between ZNF263 and OGT is crucial for activating downstream transcriptomics. We reveal that the O-GlcNAcylation site Ser662 is responsible for ZNF263 chromatin association at candidate gene promoters and OGT facilitated HCC the malignant phenotypes. Our data establish the importance of aberrant OGT and ZNF263 O-GlcNAcylation in HCC malignant progression, and represents the pursuit of OGT as a target for HCC therapy.

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