Ask about this productRelated genes to: PIAS3 antibody
- Gene:
- PIAS3 NIH gene
- Name:
- protein inhibitor of activated STAT 3
- Previous symbol:
- -
- Synonyms:
- FLJ14651, ZMIZ5
- Chromosome:
- 1q21.1
- Locus Type:
- gene with protein product
- Date approved:
- 2004-06-02
- Date modifiied:
- 2016-10-05
Related products to: PIAS3 antibody
Related articles to: PIAS3 antibody
- Brain metastasis (BrM) is the most common complication with the highest mortality in clinical tumor patients. Its underlying pathogenesis remains unclear, and effective therapeutic compounds are currently unavailable. Herein, we first revealed that S100A14 is a critical molecular mediator of tumor-derived exosomes (EVs)-driven BrM. DIA-based proteomics demonstrated consistently high S100A14 expression in BrM-EVs from both cells (53.2-fold in A549 BM3 cells and 2.4-fold in 4T1 BM2 cells) and clinical patient samples (5.1-fold). Intracardiac injection mice model confirmed that S100A14-overexpression EVs promoted BrM in breast (4T1: 88.89% vs. 44.45%; MDA-MB-231: 66.67% vs. 33.33%) and lung cancer (LLC: 50% vs. 33.33%; A549: 83.33% vs. 33.33%). Mechanistically, S100A14 directly targeted PIAS3 to reprogram astrocytes (AS) by activating STAT3 signaling and triggering secretion of pro-inflammatory chemokines (CCL2/CCL5/CXCL5), which recruit immunosuppressive MDSCs. Crucially, we identified the natural compound, germacrone, as a promising therapeutic agent that effectively inhibited BrM progression in both lung and breast cancer without significant toxicity. Germacrone directly binds to S100A14 in AS to disrupt the S100A14-PIAS3 interaction, inhibit STAT3 activation, and MDSCs recruitment. Our study elucidated a novel mechanism by which tumor-derived S100A14 EVs promote tumor BrM. Moreover, germacrone emerged as a prospective therapeutic agent for preventing BrM by specifically targeting S100A14. - Source: PubMed
Publication date: 2026/04/10
Feng QianYang XiaAn LinWang Xue-YuWang Ming-RuiCai Zhuo-HongXie Cai-JunQiao Li-JunShen You-BiLiang Xi-MinZhang RongWang Cai-YanLiu Zhong-QiuZhang Rong-Rong - To investigate the role of Benzo[a]pyrene (BaP) in driving the Correa cascade during gastric cancer development, we employed an integrated strategy combining network toxicology, machine learning, and molecular dynamics (MD) simulations. We identified 301 co-expressed genes spanning the Correa sequence, from chronic inflammation to invasive carcinoma. A protein-protein interaction network was constructed using STRING, and CytoHubba analysis highlighted five hub genes: TNF, IL6, IFNG, IL1B, and STAT3. Using CHEMBL and SUPER-PRED, we predicted 846 potential BaP targets. Intersection with disease-related genes revealed 62 common targets. Among eight candidate hub genes, an integrated Stepglm[both] and Random Forest model identified STAT3, TP53, and MMP9 as core targets. Receiver operating characteristic analysis confirmed their strong diagnostic potential (AUC > 0.78), while SHAP analysis ranked STAT3 as the most influential factor (SHAP = 0.241). Notably, these genes exhibited synergistic expression patterns in tumors (STAT3-TP53: ρ = 0.175; STAT3-MMP9: ρ = 0.261; TP53-MMP9: ρ = 0.216; all P < 0.01) and showed a dose-dependent association with disease progression. Genomic profiling revealed frequent mutations and amplifications in STAT3, TP53, and MMP9, with TP53 exhibiting the highest mutation rate. Analysis using UALCAN demonstrated significant upregulation of their mRNA levels in tumor tissues compared to normal tissues (P < 0.05). Clinically, high STAT3 and TP53 expression correlated with poorer survival, whereas elevated MMP9 levels were associated with improved outcomes. Mechanistic studies, including molecular docking and dynamics simulations, confirmed stable BaP-target interactions (e.g., STAT3 binding energy = -8.285 kcal/mol) mediated by non-covalent interactions, which disrupt the bidirectional STAT3-TP53 regulatory axis (STAT3 → MDM2 ⊣ TP53; TP53 → PIAS3 ⊣ STAT3). In summary, this study identifies STAT3, TP53, and MMP9 as central mediators of BaP-induced progression along the Correa cascade via a synergistic regulatory network. These findings provide new insights into environmental gastric carcinogenesis and highlight potential therapeutic strategies, including dual STAT3/MDM2 inhibition or MMP9 blockade. - Source: PubMed
Publication date: 2026/03/03
Tong JiajiaLiu ShiYuDu TingtingLiu WangtingJin ZiyiSi WenqingZhang BingqianChen Guangxia - Zinc, an essential trace element, is critical for maintaining the normal cardiac structure and function by regulating oxidative stress, mitochondrial homeostasis, and intracellular signaling pathways. Zinc homeostasis is maintained by a tightly coordinated network of zinc transporters and zinc-responsive sensors. Zinc transporters are classified into two functionally opposing families: the SLC39A/ZIP family imports zinc into the cytosol, whereas the SLC30A/ZnT family promotes zinc efflux from the cytosol. Dys-expression or dys-functions of these transporters is implicated in the pathology of various cardiovascular diseases, including ischemia/reperfusion (I/R) injury, diabetic cardiomyopathy (DCM)), hypertrophy, and atrial fibrillation. Key transporters such as ZIP2, ZIP7, ZIP8, ZIP13, ZIP14, ZnT1, and ZnT5 perform distinct and context-dependent functions in cardiac physiology and pathpysiology. In addition, zinc-responsive sensors such as PIAS3 sense fluctuations in intracellular free zinc levels and rapidly trigger adaptive transcriptional programs that modulate expression of zinc transporters to restore zinc homeostasis. This review summarizes current advances in the understanding of zinc dyshomeostasis in cardiac pathophysiology, and highlights the emerging roles of zinc transporters as potential modulators and therapeutic targets in cardiovascular diseases. - Source: PubMed
Publication date: 2026/02/18
Cheng XinxinZhao HuanhuanZhang QiXu Zhelong - SLE is a chronic autoimmune disease characterized by immune system dysregulation, including aberrant activation of B and T lymphocytes and overproduction of proinflammatory cytokines such as IL-21. Through the STAT3 signaling pathway, this cytokine plays a key role in SLE-promoting autoantibody production and immune imbalance. It has been reported that miRNAs, such as miR-155 and miR-21, could be overexpressed in SLE and contribute to the STAT3 pathway dysregulation. We aimed to analyze the association between miR-155 and miR-21 and the expression of , , , and in PBMC from SLE patients. - Source: PubMed
Publication date: 2026/02/02
Espinoza-García NoemíPalafox-Sánchez Claudia AzucenaDe Arellano Adrián RamírezSalazar-Camarena Diana CelesteRocío Félix-Murray KatyaMarín-Rosales MiguelOrtiz-Lazareno Pablo CVega-Cornejo GabrielArmendariz-Borunda JuanMuñoz-Valle José Francisco - Immune checkpoint inhibitors have transformed melanoma therapy but frequently cause immune-related adverse events (irAEs), including colitis, that limit treatment. Reliable biomarkers predicting toxicity remain lacking. - Source: PubMed
Publication date: 2026/01/27
Reschke RobinBudde PetraZucht Hans-DieterMangana JohannaDummer ReinhardPfoehler ClaudiaWistuba-Hamprecht KilianWeide BenjaminHakim-Meibodi Lara-ElenaMeier FriedegundSchulz CarstenRichter JasminBräutigam ManualGutjahr ClaudiaSchulz-Knappe PeterHassel Jessica C