TNFAIP8 (TNF Alpha Induced Protein 8)

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.

Through comprehensive clinical cohorts and functional investigations, the present study identified TIPE2 as a clinically significant prognostic biomarker and revealed its potential role in regulating integrin-mediated oncogenic processes in cholangiocarcinoma. Therapeutic enhancement of TIPE2 expression emerges as a promising precision medicine strategy for cholangiocarcinoma management.

Cross-organ single-cell integration prioritizes liver-selective stromal circuitry and nominates hepatocyte-FB axes (HGF-MET, AGT-AGTR1B) as plausible links between fibrogenic remodeling and a pro-tumorigenic niche, yielding testable hypotheses at the interface of regeneration, RAS biology, and tumor initiation.

Pan-lactylation levels in retinal tissue were assessed by Western Blot and markedly upregulated in adult TIPE2-/- retinas. These findings demonstrate that TIPE2 deficiency was associated with retina hypoperfusion and age-related retinal thinning, suggesting that TIPE2 plays an essential role in preserving the natural state of retina.

Further experiments demonstrated that si-TNFAIP8 reduced the mRNA and protein levels of ATG3. Co-IP verified TNFAIP8 interacts with ATG3.TNFAIP8 may regulate AS autophagy by targeting ATG3.

RNA interference and overexpression of TNFAIP8L induced the expression of immune-related genes Toll, Serpin, B-cell lymphoma (Bcl), Lectin, Defensin, Crustin, and anti-lipopolysaccharide factor (ALF) in hemocytes and gills. Together, the results suggest that TNFAIP8L mediates immune responses in P. clarkii.

TIPE3 expression is elevated in breast cancer and likely promotes breast cancer growth and metastasis through the AKT-GSK3β-β-catenin/Snail pathway. TIPE3 may be a novel therapeutic target for breast cancer.

Drug repurposing analysis prioritized 13 candidates targeting these proteins, including FDA-approved agents, and PheWAS supported their safety. This study provides the first genetic evidence supporting the causal roles of TNFAIP8, TCL1A, WFDC1, and TNFSF8 in AML, offering new insights for targeted therapy development and biomarker-based disease monitoring.

Rescue experiments with recombinant ubiquitin protein (Ub) and the ubiquitination inhibitor MG132 demonstrated that F-box and WD repeat protein 1A (FBW1A)-mediated ubiquitination of NLRP3 and C1qbp is required in TIPE2 deficiency-induced pyroptosis, mitochondrial damage and oxidative stress. Overexpression of TIPE2 suppressed NLRP3-mediated pyroptosis and C1qbp-mediated oxidative stress and improved respiratory function and pulmonary tissue damage in vivo. TIPE2 protects asthmatic bronchial epithelial cells from NLRP3-induced pyroptosis and C1qbp-induced oxidative stress by interacting with the E3 ubiquitin ligase FBW1A in vitro and in vivo.

Pharmacological TNFAIP8 inhibition represents a viable therapeutic strategy for mitigating chemotherapy-induced cardiac dysfunction. Future investigations should prioritize developing cardiac-targeted TNFAIP8 inhibitors and validating their efficacy in large-animal DIC models.

Combined expression of TIPE3 and RAC1 improved risk stratification and prognostic prediction in LUAD. TIPE3 and RAC1 serve as potential biomarkers of tumor progression and poor prognosis in LUAD, offering promising targets for future therapeutic interventions.

Our findings indicate that the risk model associated with mitochondrial metabolism may serve as a dependable prognostic indicator, facilitating tailored therapeutic strategies for CRC patients. TMEM86B promotes colorectal cancer progression, and its downregulation inhibits tumor growth in vitro and in vivo.