FOXO3
- Known as:
- FOXO3
- Catalog number:
- 000062A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- FOXO3
Related genes to: FOXO3
- Gene:
- FOXO3 NIH gene
- Name:
- forkhead box O3
- Previous symbol:
- FKHRL1, FOXO3A
- Synonyms:
- AF6q21, FOXO2
- Chromosome:
- 6q21
- Locus Type:
- gene with protein product
- Date approved:
- 1998-03-23
- Date modifiied:
- 2015-08-25
Related products to: FOXO3
Related articles to: FOXO3
- Background Anti-programmed cell death protein-1 (anti-PD-1) immunotherapy has transformed the treatment of advanced melanoma, but durable benefit remains limited to a subset of patients. CD8+ T cell exhaustion contributes to immune escape in the melanoma tumor microenvironment, while the post-transcriptional regulation of exhaustion-associated genes by microRNAs (miRNAs) remains incompletely understood. Objective We characterized miRNA-mRNA regulatory associations in CD8+ T cell exhaustion-enriched melanoma transcriptomes, classified inverse associations as loss-of-repression (LoR) or active suppression (AS), extended the network to candidate long non-coding RNA (lncRNA)-miRNA-mRNA relationships, and examined whether network-derived transcriptomic scores were associated with anti-PD-1 outcomes in independent cohorts. Methods The TCGA-SKCM bulk transcriptomes were filtered by single-sample gene set enrichment analysis (ssGSEA), yielding 121 CD8+ T cell exhaustion-enriched cases and 115 cases with paired miRNA and mRNA measurements. Differentially expressed miRNAs (DEmiRNAs) were identified between fixed high- and low-exhaustion tertiles (n = 38 each) using two-sided Mann-Whitney U tests with Benjamini-Hochberg correction (|log₂FC| ≥ 0.5; false discovery rate (FDR) ≤ 0.05). Database-supported inverse Spearman's correlations (ρ ≤ -0.30; FDR ≤ 0.05) were assembled into a bipartite network. Edges were classified as LoR or AS, and a competing endogenous RNA (ceRNA) extension incorporated DIANA-LncBase/ENCORI lncRNA-miRNA interactions. Nine biologically anchored axes underwent continuous-score analysis and HC3 regression adjusted for tumor purity, CD8, fibroblast/CAF, myeloid, interferon-gamma, and sample type, together with four sensitivity analyses. Exploratory clinical testing used GSE78220 and the pre-PD-1 biopsy subset of the DFCI melanoma cohort (cBioPortal study identifier: mel_dfci_2019). Results Twenty-six DEmiRNAs (20 upregulated and 6 downregulated) formed 326 inverse miRNA-mRNA edges, comprising 263 AS and 63 LoR associations. Six of nine focused axes met the adjusted-support criterion, and all six were AS-classified including upregulated miR-155-5p as the dominant hub, with inverse associations involving FOXO3 (= -0.305, adjusted p = 0.020) and MEIS1, the strongest priority edge (= -0.470, adjusted p < 0.0001). NEAT1, MALAT1, and XIST emerged as the top-degree lncRNA hubs, all classified as AS-sponge type. Exclusion of one solid-tissue-normal specimen left 114 paired tumors, retained 25 DEmiRNAs, and supported seven of nine axes in the tumor-only sensitivity analysis. Relational integration with lncRNA-miRNA records yielded 29,274 candidate chains, including 790 containing a focused miRNA-mRNA edge. Transcriptomic score analyses were negative and exploratory in GSE78220 (mRNA proxy area under the curve (AUC) = 0.631; Mann-Whitney p = 0.269) and in the DFCI melanoma cohort (mRNA topology AUC = 0.453, p = 0.451; lncRNA topology AUC = 0.388, p = 0.0695). Conclusions The LoR/AS framework offers a transparent means of organizing correlative miRNA-mRNA hypotheses in melanoma bulk transcriptomes. The adjusted results favored an AS pattern among the focused axes, but they did not establish CD8+ T-cell-intrinsic regulation, direct miRNA targeting, ceRNA activity, or clinical predictive utility. Experimental testing in sorted or single-cell melanoma CD8+ tumor-infiltrating lymphocyte systems is required. - Source: PubMed
Publication date: 2026/08/20
Javed Muhammad Zain UHussain Muhammad - MicroRNA-122 (miR-122) is the most abundant liver-specific microRNA, comprising ~ 70% of the hepatic miRNA pool, and a central regulator of lipid metabolism, inflammation, fibrosis, viral replication, and hepatocarcinogenesis. This review synthesizes experimental, clinical, and molecular evidence on the role of miR-122 across the spectrum of liver disease, including metabolic dysfunction-associated fatty liver disease (MAFLD) and steatohepatitis (MASH), drug-induced acute liver injury, hepatitis B and C virus (HBV/HCV) infection, hepatocellular carcinoma (HCC), and colorectal cancer liver metastasis. Mechanistically, miR-122 governs hepatic lipogenesis through the Sirt1/LKB1/AMPK axis, modulates inflammation via LPS/TLR-4/FoxO3 signaling, and exerts tumor-suppressive and antiviral effects through Cyclin G1/p53, HO-1, NDRG3, GALNT10, PEG10, and NEGR1. A recurring theme is the compartment- and stage-dependent behavior of miR-122: hepatic expression declines with disease progression, whereas circulating levels rise with hepatocyte injury, reconciling apparently contradictory reports and underscoring the importance of specimen source and disease stage in biomarker interpretation. We further contrast the etiology-specific regulation of miR-122 in HBV- versus HCV-associated disease, in which epigenetic silencing and interferon-linked mechanisms drive divergent expression. Finally, we critically appraise the failed clinical translation of anti-miR-122 therapeutics (miravirsen, RG-101), highlighting viral resistance, safety liabilities, and the tumor-suppressor paradox that constrains inhibition-based strategies. Collectively, miR-122 emerges as a minimally invasive biomarker and a biologically informative, though therapeutically challenging, target in liver disease. - Source: PubMed
Publication date: 2026/09/19
Ahmadova SaraWicik ZofiaMucha JoannaPalatini JeffZiętal KatarzynaMirowska-Guzel DagmaraPrzybylkowski AdamEyileten Ceren - Intestinal dendritic cells (DCs) play a central role in maintaining gut tolerance through priming of peripheral regulatory T cells (pT cells). DC tolerogenicity has been linked to catabolic metabolism, but the role of AMP-activated kinase (AMPK), a key regulator of catabolic metabolism, in regulating intestinal tolerance remains unclear. We found high AMPK activation in intestinal DCs, and loss of AMPKα1 in CD11c-expressing cells (CD11c) led to reduced frequencies of intestinal RALDH CD103 cDC2s. This was associated with reduced pT cell induction and consequently increased type 2 immunity in models of intestinal helminth infection. Correspondingly, CD103 cDC2s from helminth-infected CD11c mice failed to prime T cells ex vivo. Similarly, T cell induction by AMPK-deficient human retinoic acid (RA)-induced tolerogenic CD103 DCs was compromised. Mechanistically, AMPK underpinned RA-driven tolerogenicity by promoting RALDH activity and TGF-β secretion in a FoxO3-dependent manner, independent from metabolic reprogramming. Our findings identify AMPK as a key regulator of intestinal DC-mediated tolerance and as a therapeutic target to counter intestinal inflammatory disease. - Source: PubMed
Publication date: 2026/09/16
Patente Thiago Avan Duijvenvoorde JulianHeieis Graham ABrombacher Eline CPelgrom Leonard RLambooij JoostZawistowska-Deniziak AnnaErbì MartinaOtto FrankOzir-Fazalalikhan ArifaBarnhoorn SaraFernández José Jvan der Reijden Johanvan der Ham Alwin JHawinkels Lukas J A CGuigas Bruno ABarbuto José A MMaizels Rick MEverts Bart - Apical periodontitis (AP) is an infectious disorder characterized by periapical inflammation and alveolar bone destruction. Recent evidence suggests that cuproptosis, a distinctive form of copper-regulated cell death, has been implicated in the regulation of bone loss. This study aimed to investigate the involvement of cuproptosis and its mechanism in modulating bone loss in AP. - Source: PubMed
Publication date: 2026/09/16
Zhang KaiyingMa ZhenshengWen BoCui HaoMa Dandan - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron loss, skeletal muscle atrophy, paralysis, and eventually death. Mitochondrial dysfunction plays a pivotal role in ALS pathogenesis, although the precise pathogenic mechanisms remain elusive, and effective therapeutic strategies are extremely limited. In this study, we developed a small-molecule inhibitor, UA-30, which directly targets RalA, and explored its potential for the treatment of ALS. We found that when administered via oral gavage for 6 weeks following the onset of motor deficit, UA-30 extended lifespan and improved motor function of SOD1G93A mice, a model of ALS. UA-30 ameliorated motor neuron loss, neuroinflammation, fibrosis, and mitochondrial dysfunction, as evidenced by energy recovery, decreased oxidative stress, and enhanced mitophagy. Mechanistically, UA-30 inhibited RalA activity and thereby modulated ERK/FOXO3a signaling, which inhibited FOXO3a degradation via the ubiquitin-proteasome pathway; enhanced FOXO3a stability; and upregulated the expression of mitophagy-related genes in this ALS mouse model. The beneficial effects of UA-30 in ALS were abolished by overexpression of the constitutively active form of RalA (RalAG23V) or Mdivi-1 treatment. These findings support RalA inhibition as a therapeutic strategy for enhancing mitophagy and mitigating ALS-like pathology and support UA-30 as an orally active candidate for further preclinical development. - Source: PubMed
Publication date: 2026/09/15
Zhang BinggeHe YeSu TingLi XiaomeiZhang XiufenLiu RuijuanHan XiaoZhang RuimingYang ChaoLiu XinleiHou QinghuaZhang ZaijunXie YongmeiLiu GongpingYang Xifei