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Effect of depletion of USP16 on gene expression of HGC-27 cells

ABSTRACT: Gastric cancer has emerged as one of the malignant tumors with increasing incidence in recent years, posing significant challenges to global health. However, effective targeted therapies for gastric cancer remain limited. Despite strict Hippo pathway regulation, the oncoprotein YAP is frequently overexpressed in gastric cancer, indicating that mechanisms beyond phosphorylation must exist to control YAP stability. In this study, we focus on the impact of YAP deubiquitination on the progression of gastric cancer. Our study identifies USP16 as a novel deubiquitinase of YAP and demonstrates it as a direct therapeutic target of ISO in gastric cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE316152 | GEO | 2026/01/15

REPOSITORIES: GEO

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	GSE316152_gene_fpkm.csv.gz	Csv

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Genome-wide maps of Usp16, ubH2A and gene expression profiles in wild type and Usp16 knock out mouse embryonic stem cells (ESCs) and embryoid bodies (EBs)

Project description:Polycomb Repressive Complex 1 and histone H2A ubiquitination (ubH2A) contribute to embryonic stem cell (ESC) pluripotency by repressing lineage-specific gene expression. However, whether active deubiquitination co-regulates ubH2A levels in ESCs and during differentiation is not known. Here, we report that the histone H2A deubiquitinase Usp16 regulates H2A deubiquitination and gene expression in ESCs, and importantly, is required for ESC differentiation. Usp16 knockout is embryonic lethal in mice, but does not affect ESC viability or identity. Usp16 binds to the promoter regions of a large number of genes in ESCs and Usp16 binding is inversely correlated with ubH2A levels and positively correlated with gene expression levels. Intriguingly, Usp16-/- ESCs fail to differentiate due to ubH2A-mediated repression of lineage-specific genes. Finally, Usp16, but not the enzymatically inactive mutant, rescues the differentiation defects of Usp16-/- ESCs. Therefore, this study identifies Usp16 and H2A deubiquitination as critical regulators of ESC gene expression and differentiation. Examination of binding pattern of H2A deubiquitinase Usp16 and ubH2A in mouse embryonic stem cells and embroid bodies

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