TRIM21 (Tripartite Motif Containing 21)

Our findings demonstrate that IFI35-TRIM21-HNF4α axis may play a crucial role in TNF-α and IFN-γ induced suppression of HBV. Consequently, these results reveal a novel antiviral action of IFI35 against HBV. These findings may hold value in the development of alternative anti-HBV drugs.

In breast cancer models, pharmacologic engagement of TRIM21 with fenretinide decreases PD-L1 palmitoylation, reprograms the tumor microenvironment toward cytotoxic immunity, restores antitumor responses, and improves anti-PD-1 efficacy. Collectively, these results indicate that HILPDA-driven lipogenesis increases PD-L1 palmitoylation, leading to immune evasion and ICB resistance, and TRIM21/HILPDA-targeted combinations are proposed as a therapeutic strategy.

Clinical analysis further establishes that elevated PSMD14 and BCKDK expression in GBM correlates with decreased CD8+ T and NK cell infiltration and poorer patient survival. These findings highlight the PSMD14-BCKDK axis as a central regulator of tumor metabolic adaptation and immune suppression, and support PSMD14 inhibition-alone or in combination with CAR-NK therapy-as a promising strategy for precision immunometabolic intervention in GBM.

Pharmacological inhibition of ferroptosis modulated TRIM21/USP4-linked phenotypes and corresponding ferroptosis-related indices. These findings identify TRIM21 as a clinically relevant regulator that links USP4/TGF-β-associated signaling to ferroptosis-related homeostasis, thereby promoting malignant behaviors in colorectal cancer and providing a targetable vulnerability for therapeutic development.

The TRIM21-FBL axis regulates ccRCC progression by modulating PI3K/AKT signaling, providing mechanistic insight and potential therapeutic targets for ribosome biogenesis and oncogenic signaling.

Clinically, CASP expression was correlated with mismatch repair (MMR)/microsatellite instability (MSI) status and TP53 mutational profiles. These findings implicate CASP in CRC progression and support its potential as a prognostic biomarker and therapeutic target by disrupting CASP-driven signaling.

In orthotopic models, TNFAIP8 silencing or lipid nanoparticle-mediated shTNFAIP8 delivery reduced fibrosis, suppressed tumor progression, and enhanced gemcitabine efficacy without evident toxicity, suggesting the feasibility of a therapeutic approach. These findings uncover a mechanistic framework linking metabolic dysregulation to fibroinflammatory remodeling in PDAC, and nominate TNFAIP8 as a promising stromal-targeted therapeutic candidate.

Our study unveils the SIRT1/p300-Beclin-1-TRIM21 axis as a key nutrient-sensing pathway that promotes bladder cancer metastasis through crosstalk between acetylation and ubiquitination. These findings identify new therapeutic vulnerabilities in advanced bladder cancer.

Consequently, SNHG18 deficiency fosters an immunosuppressive TME and promotes PCa BM. SNHG18 expression may serve as a predictive biomarker for ICB response, offering a novel strategy to overcome immunotherapy resistance in PCa BM.

Notably, treatment with ENMD-2076 (identified through Connectivity Map analysis) significantly reduced KIF20A expression, attenuated CSC characteristics, augmented cisplatin sensitivity, and exerted marked antitumor activity. These findings elucidate a novel KIF20A-DHX9-SOX2 regulatory axis that simultaneously governs CSC maintenance and ferroptosis evasion in OSCC. Targeting KIF20A, either as a monotherapy or in combination with chemotherapy, may offer a promising strategy to improve therapeutic outcomes in OSCC.

Our findings reveal a previously unrecognized role for fenofibrate in augmenting EZH2-targeted therapy. This study provides a novel strategy to improve the efficacy of epigenetic therapies in cancer by combining EZH2 inhibitors with fenofibrate, offering potential clinical benefits for precision oncology.

Crucially, clinical analysis reveals that high levels of OGT, POM121, and c-MYC positively correlate with adverse clinical outcomes. These findings establish the OGT-POM121-c-MYC-ECM axis as a potential diagnostic biomarker and a promising therapeutic target for NSCLC bone metastasis.