Ask about this productRelated genes to: UGT8 antibody
- Gene:
- UGT8 NIH gene
- Name:
- UDP glycosyltransferase 8
- Previous symbol:
- CGT
- Synonyms:
- -
- Chromosome:
- 4q26
- Locus Type:
- gene with protein product
- Date approved:
- 1996-10-02
- Date modifiied:
- 2017-12-15
Related products to: UGT8 antibody
Related articles to: UGT8 antibody
- Ceramide galactosyltransferase (UGT8) is overexpressed in basal-like breast cancer (BC) tumors and is associated with an increased risk of lung metastasis. UGT8 synthesizes galactosylceramide (GalCer), an anti-apoptotic molecule that promotes BC cell survival within the tumor microenvironment and enhances resistance to anticancer drugs. In this study, we aimed to elucidate the molecular mechanisms underlying UGT8 overexpression in BC cells. UGT8 promoter constructs and deletion mutants were generated by PCR. Promoter activity was assessed using a dual-luciferase assay, and key regulatory sequences were identified by electrophoretic mobility shift assay (EMSA). Candidate transcription factors were predicted using the JASPAR database and validated by qPCR, Western blotting, and immunohistochemistry. GalCer levels were measured by thin-layer chromatography (TLC) binding assay, and LHX6-DNA interactions were analyzed by surface plasmon resonance. Apoptotic cells were detected using the Thermo Dead Cell Apoptosis Kit. UGT8 promoter activity was significantly higher in UGT8-positive MDA-MB-231 cells than in UGT8-negative T47D and MCF-7 cells, indicating that UGT8 gene expression is regulated at the transcriptional level. Sequential promoter deletions combined with EMSA localized a key regulatory region (- 1132 to - 1618 bp), termed the UGT8 response element (UGT8RE). In silico analysis identified potential transcription factors, among which the LIM/homeobox protein LHX6 was markedly upregulated in MDA-MB-231 cells. Site-directed mutagenesis of two predicted LHX6 binding sites (LHX6BS1 and LHX6BS2) demonstrated that LHX6BS2 is essential for UGT8 promoter activity. RNAi-mediated inhibition of LHX6 reduced UGT8 expression and GalCer synthesis, thereby sensitizing MDA-MB-231 cells to doxorubicin-induced apoptosis. The LIM/homeobox protein LHX6 may regulate the UGT8 expression in BC cells. Targeting LHX6 decreases UGT8 expression and GalCer synthesis, thereby sensitizing MDA-MB-231 cells to doxorubicin. Given UGT8's role in cell survival and drug resistance, inhibition of LHX6 may represent a promising therapeutic strategy for drug-resistant BC. - Source: PubMed
Publication date: 2026/03/04
Suchanski JaroslawWoldanska WeronikaNour Ebad SafouraGrzymajlo KrzysztofPiotrowska AleksandraOwczarek Tomasz BRomanowicz HannaSmolarz BeataDziegiel PiotrUgorski Maciej - Urolithiasis is a complex disease influenced by genetic and metabolic factors. Although genome-wide association studies (GWAS) have identified susceptibility loci, the causal genes and mechanisms remain unclear. This study aimed to identify genes whose genetically regulated expression contributes to urolithiasis risk and clarify their potential biological roles. We integrated two independent European-ancestry GWAS datasets with multi-tissue expression quantitative trait loci (eQTL) data from genotype-tissue expression project (GTEx) V8. Cross-tissue and single-tissue transcriptome-wide association studies, conditional and joint analyses, gene-level association, and fine-mapping were applied to prioritize candidate genes. Mendelian randomization and Bayesian colocalization were used to assess causality and shared genetic signals. Functional networks were explored using GeneMANIA. Multi-layer analyses identified GCAT and UGT8 as independent causal genes. MR analyses confirmed significant causal effects, supported by colocalization (PPH4 > 0.80). GCAT regulates glycine metabolism and oxalate production, linking systemic metabolic status to urinary microenvironment, whereas UGT8 modulates glucuronidation in fibroblasts, influencing local metabolic conditions relevant to stone formation. This study establishes GCAT and UGT8 as causal genes for urolithiasis, providing mechanistic insight into glycine/oxalate metabolism and glucuronidation pathways. These findings expand understanding of genetic regulation in stone formation and highlight potential targets for preventive and therapeutic interventions. - Source: PubMed
Publication date: 2026/02/12
Zhu GuangqiangTan ChunlinLi Yugen - Mercury (Hg) remains a prominent global contaminant despite regulatory interventions such as the Minamata Convention. Inorganic mercury (Hg), particularly mercuric chloride (HgCl), persists in aquatic ecosystems and poses significant risks to both environmental and human health. While its neurotoxicity is well recognized, the systemic interplay between brain and liver responses under sub-lethal exposure remains poorly understood. Here, we exposed zebrafish () to an environmentally relevant concentration of HgCl (0.04 ppm) for 15 days to examine behavioral, neurochemical, molecular, and hepatic alterations. Mercury exposure induced pronounced anxiety-like behavior and delayed social recognition, accompanied by decreased locomotor activity. These behavioral deficits are supported with depletion of dopamine, serotonin, and acetylcholinesterase activity, implicating disrupted monoaminergic and cholinergic signaling. Molecular profiling revealed downregulation of and , indicating glial dysfunction, and upregulation of , consistent with neuroinflammation. In the liver, mercury triggered a shift toward apoptosis (/ ratio increase), inflammation ( elevation), and loss of junctional integrity ( downregulation). Biochemically, exposure to HgCl elevated serum SGPT levels, enhanced lipid peroxidation, and caused dyslipidaemia characterized by reduced HDL, triglyceride, and cholesterol levels. Immunohistochemistry confirmed strong hepatic Hsp90 overexpression, marking oxidative and proteotoxic stress, while histological analysis revealed steatosis, parenchymal disorganization, and nuclear pyknosis. Together, these findings establish that even low-level inorganic mercury exposure perturbs both central and peripheral systems through convergent oxidative and inflammatory mechanisms. Our study highlights mercury as a systemic toxicant disrupting the liver-brain axis and underscores the importance of integrating multi-organ endpoints in environmental risk assessment of heavy metals. - Source: PubMed
Publication date: 2026/01/28
Shaikh AfridiRana NancyGupta AyushiTilak NandiniKachaliya UzmaRoy Hetal - Sunitinib has marked pharmacokinetic (PK) and pharmacodynamic (PD) interpatient variability. This study evaluated the utility of extensive excretory/metabolic/PD pharmacogenomics (PGx) with hepatic functional imaging (HNI) to explore their associations with sunitinib PK/PD (toxicity/response) and progression-free survival (PFS), respectively. - Source: PubMed
Publication date: 2026/01/04
Michael MichaelToner Guy CGanju VinodLink EmmaThompson MickMatera AnettaHicks Rodney JCampbell IanRowley SimoneKarapetis Christos SBurge MatthewPook David W - Peripheral nerve injuries occur due to accidents and in manufacturing every day. Unlike the central nervous system, injured peripheral nerves can self‑regenerate after injury. The study explored changes in gene expression and related biological processes after peripheral nerve injury and regeneration. Male Sprague‑Dawley rats were divided into six groups and underwent sciatic nerve resection followed by recovery for 0, 3, 6, 10, 15, and 20 days; distal sciatic nerve segments were collected for sequencing, real‑time quantitative polymerase chain reaction (RT‑qPCR), and Western blotting. According to DNA microarray analysis, approximately 5,000 genes were differentially expressed, and six biological processes were identified at different time points after nerve transection, with expression mainly observed in the mid and latter stages after injury. Four genes (UDP glycosyltransferase 8 [Ugt8], C‑C motif chemokine ligand 2 [Ccl2], neuregulin 1 [Nrg1], and heme oxygenase‑1 [Hmox1]) with nerve regeneration‑specific function were selected for further verification using RT‑qPCR and Western blot. The results demonstrated that genes such as Ugt8 decreased initially and then peaked at 20 days, whereas Ccl2 and Hmox1 both exhibited two peaks at three and 20 days. Nrg1 showed a gradual increase, peaking around 15 days. The study identified differential gene expression in distal nerve segments during Wallerian degeneration and analyzed the associated dynamic biological changes. The findings provide insights into research on peripheral nerve injury and regeneration, and further studies will involve screening key genes and more detailed investigations. - Source: PubMed
Publication date: 2025/12/27
Wang ZhengmingHe YichunGuo YushanTang TiantianJiang Nan