ArticleOncoimmunology2025
Deubiquitinating enzyme JOSD2 modulates cGAS to facilitate immune evasion in colorectal cancer.
Article in Oncoimmunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Development and validation of a prediction model for 6-month early death in pediatric H3K27M-mutant diffuse intrinsic pontine glioma (DIPG).Translational pediatrics · 2026Article
- Targeting the Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Pathway: An Emerging Therapeutic Strategy for Digestive Diseases.Clinical and translational gastroenterology · 2026Review
- Multidimensional analysis of deubiquitinating enzymes in colorectal cancer: biological mechanisms and targeted therapeutic strategies.Frontiers in oncology · 2026Review
- cGAS-STING signaling: a therapeutic target in inflammatory bowel disease and related colorectal cancer.Frontiers in immunology · 2025Review
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colorectal cancer (CRC) remains a formidable clinical challenge, many patients exhibit limited responses to conventional chemotherapy and targeted therapies. Although immunotherapy has demonstrated potential, its efficacy is largely restricted to a subset of patients with high microsatellite instability (MSI-H), highlighting the critical need to identify key molecular drivers of immune evasion in CRC. Through comprehensive bioinformatic analysis, we identified the deubiquitinating enzyme JOSD2 as a key player in CRC progression, with elevated expression correlating with poor prognosis in MSI-H patients (HR = 4.79, 95% CI: 3.6-7.96) and dysregulation of multiple immune-related pathways. Mechanistically, we discovered that JOSD2 suppresses cGAS enzymatic activity by removing K27-linked ubiquitination, thereby promoting M2 polarization of macrophages, a process critical for immunosuppression in the tumor microenvironment. Furthermore, using the JOSD2 catalytic inhibitor HY041004, we demonstrated both
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