AKR1C3 _ DDH3
- Known as:
- AKR1C3 _ DDH3
- Catalog number:
- EB06637
- Product Quantity:
- 0.1 mg
- Category:
- -
- Supplier:
- ACR
- Gene target:
- AKR1C3 _ DDH3
Related genes to: AKR1C3 _ DDH3
- Gene:
- AKR1C3 NIH gene
- Name:
- aldo-keto reductase family 1 member C3
- Previous symbol:
- HSD17B5
- Synonyms:
- KIAA0119, DDX, HAKRB, PGFS
- Chromosome:
- 10p15.1
- Locus Type:
- gene with protein product
- Date approved:
- 1998-09-29
- Date modifiied:
- 2016-10-05
Related products to: AKR1C3 _ DDH3
Related articles to: AKR1C3 _ DDH3
- Parkinson's disease (PD) is a complex neurodegenerative disorder in which environmental toxins play a critical etiological role. Rotenone, a classical mitochondrial complex I inhibitor used to model PD, exerts its neurotoxicity through incompletely defined downstream molecular networks. Here, we integrated multiple PD transcriptomic datasets from GEO with predicted rotenone targets, applied machine learning to screen core candidate genes, and analyzed their cellular localization using single-cell transcriptomics. Molecular docking was performed to assess target-rotenone binding, and functional validation was carried out in primary dopaminergic neurons via lentivirus-mediated gene manipulation, Western blotting, qRT-PCR, and mitochondrial function assays. This approach identified and validated a six-gene core network (AKR1C2, AKR1C3, CES1, CTSS, DRD2, HSPA1A), several of which were predicted to directly bind rotenone. Single-cell analysis confirmed their enrichment in PD dopaminergic neurons, and immunofluorescence validated their co-localization with the dopaminergic marker TH. In rotenone-treated neurons, all six genes except DRD2, as well as KRT8, were significantly upregulated at both the mRNA and protein levels; rotenone also impaired mitochondrial Complex I activity and ATP production, and increased α-synuclein expression. In silico knockout revealed that AKR1C2-perturbed genes were enriched in keratinization pathways. Functional experiments demonstrated that AKR1C2 positively regulates KRT8. Notably, AKR1C2 knockdown not only reduced KRT8 levels but also rescued mitochondrial function, neuronal viability, and rotenone-impaired action potential firing, whereas AKR1C2 overexpression exacerbated these deficits. Critically, KRT8 re‑expression reversed the protective effects of AKR1C2 knockdown, while KRT8 knockdown reversed AKR1C2 overexpression‑induced impairments, collectively confirming the causal role of the AKR1C2-KRT8 axis. Collectively, these findings delineate a multi-node molecular network downstream of rotenone and provide the first experimental validation of a novel AKR1C2-KRT8 regulatory axis in dopaminergic neuron injury. - Source: PubMed
Publication date: 2026/09/01
Lin JianheHe LianyuWang JinglingYang CuiyuLiang ShushuHuang JinshanLi SijunZheng DengxingLiang Mei - Ochratoxin A (OTA), a food-borne mycotoxin, has been implicated in hepatotoxicity and potential carcinogenic processes, yet the molecular links between OTA exposure and hepatocellular carcinoma (HCC) remain incompletely understood. This study used an integrated computational workflow to prioritize candidate targets and pathways potentially linking OTA exposure with HCC. OTA-related and HCC-related targets were collected from public databases, intersected, and subjected to functional enrichment analysis. Transcriptomic data from the GSE36376 discovery dataset were analyzed to identify differentially expressed genes, followed by LASSO and SVM-RFE feature selection, immune-cell deconvolution, molecular docking, and molecular dynamics simulation. A total of 214 overlapping OTA-HCC-associated targets were identified and were enriched in pathways related to signal transduction, apoptosis, metabolism, and immune regulation. In GSE36376, 443 differentially expressed genes were identified using p < 0.05 and |log2 fold change| > 1, and overlap analysis yielded 13 shared target genes. Five candidate targets, CYP3A4, KIFC1, AKR1C3, CA2, and TTR, were further prioritized. KIFC1 and AKR1C3 were upregulated in HCC samples, whereas CYP3A4, CA2, and TTR were downregulated. These genes showed apparent discriminatory ability within the discovery dataset, with AUC values ranging from 0.866 to 0.958. Molecular docking predicted favorable OTA-target interactions, with docking energies ranging from -7.4 to -10.8 kcal/mol. CYP3A4 showed the lowest predicted docking energy (-10.8 kcal/mol) and was further evaluated by molecular dynamics simulation, with a protein-fitted OTA RMSD of 1.435 ± 0.097 nm and complex Rg of 2.308 ± 0.010 nm during the equilibrated 20-100 ns trajectory. Overall, this study provides a reproducible hypothesis-generating framework for exploring potential metabolic, genomic-instability-related, and immune-microenvironment links between OTA exposure and HCC. Future validation in independent datasets and experimental models will be important to further assess the biological relevance of these candidate targets and pathways. - Source: PubMed
Publication date: 2026/08/31
Yang ShiliLiu HuaiquanKou HaiyangLai LingyanZhang XinyanXu YunlingSun YuChen Bo - Triphala is a traditional three-fruit formulation with potential anticancer activity, but its ferroptosis-related mechanisms in oral cancer remain unclear. We integrated network pharmacology, transcriptomic analyses, prognostic modeling, Mendelian randomization, immune and drug-response analyses, molecular docking, and in vitro validation to investigate the Triphala-ferroptosis-oral cancer axis. Fifty-eight candidate functional genes were identified, and an eight-gene signature comprising AKR1C3, CA9, EGFR, GSTA1, MAPK8, MGST1, PPARG, and RB1 showed prognostic value across multiple cohorts. Mendelian randomization supported causal associations of MAPK8, MGST1, and PPARG with oral cancer risk. Seven Triphala-derived compounds, including epigallocatechin gallate, quercetin, kaempferol, luteolin, ellagic acid, gallic acid, and quinine, displayed favorable predicted interactions with key targets. In CAL-27 cells, Triphala altered the expression of signature genes, reduced GPX4 and SLC7A11 protein levels, increased Feand malondialdehyde, depleted glutathione and glutathione peroxidase activity, and enhanced lipid peroxidation; these effects were partially modulated by ferrostatin-1. This study advances the field by linking Triphala to a ferroptosis-based prognostic framework and experimentally demonstrating its regulation of the SLC7A11-GSH-GPX4 axis in oral cancer. - Source: PubMed
Zhao YiweiLi SiminJiang LinxinKreher DeborahSchmalz GerhardFichter AndreasHu Xianda - Globally, myocardial infarction (MI) remains a major cause of morbidity and mortality. Macrophage-mediated inflammation and ferroptosis-related stress responses have both been implicated in MI; however, transcriptomic identification of macrophage- and ferroptosis-related candidate genes requires rigorous control of false-positive findings. In this revised study, two peripheral blood transcriptomic datasets, GSE29532 and GSE48060, were integrated after probe annotation, independent normalization, merging based on common genes, and ComBat batch correction. Batch-correction quality was evaluated using both visualization and quantitative metrics. Differential expression analysis was performed using the limma package with adj.P.Val < 0.05 as the primary threshold. A total of 213 differentially expressed genes were identified, including 101 upregulated and 112 downregulated genes. Intersecting FDR-supported DEGs with macrophage-related and ferroptosis-related gene sets identified seven primary MFRDEGs: SMAD7, MMD, PTPN6, DDIT3, AKR1C3, PHF21A, and ACSL1. GO enrichment analysis was interpreted as exploratory functional annotation because of the small input gene set, whereas whole-ranked-gene GSEA highlighted TNFA/NF-kB inflammatory signaling, complement-related innate immune signaling, and reactive oxygen species-related transcriptional programs. Because the revised PPI analysis did not produce reliable interactions among the seven primary MFRDEGs, candidate gene prioritization was performed instead of defining interaction-derived hub genes. ssGSEA suggested a robust neutrophil-related alteration in MI, while macrophage- and monocyte-related signatures showed trend-level changes after FDR correction. Exploratory ROC analysis was performed for selected candidate genes. RT-qPCR validation further showed that SMAD7, PTPN6, DDIT3, PHF21A, and ACSL1 were increased, whereas MMD and AKR1C3 were decreased in AMI peripheral blood samples, consistent with the transcriptomic results. These findings provide FDR-supported candidate-level evidence linking macrophage- and ferroptosis-related transcriptional alterations to immune signatures in MI and warrant further validation in larger cohorts and mechanistic studies. - Source: PubMed
Publication date: 2026/08/25
Wang GuoqinZhang ZhulinYang GuanruiWang JingMa TengGuo Shuang - Cigarette smoking is associated with a poor prognosis and reduced efficacy of androgen receptor signaling inhibitors (ARSIs) in prostate cancer patients; however, the underlying molecular mechanisms remain largely undefined. This study investigated the impact of cotinine, the stable primary metabolite of nicotine, on androgen-dependent growth and therapeutic sensitivity in human prostate cancer 22Rv1 cells. While cotinine alone did not affect basal prostate-specific antigen (PSA) levels, it significantly potentiated 5α-androstane-3,17-dione (5α-Adione)-induced PSA expression and cell proliferation. Mechanistic investigations revealed that cotinine did not modulate the expression levels of androgen-synthesizing enzymes (e.g., AKR1C3, DHRS11) and E3 ubiquitin ligases. Instead, cotinine significantly extended the protein half-life of both the full-length androgen receptor (AR) and the constitutively active splice variant AR-V7. Co-immunoprecipitation assays indicated that cotinine increased the association between AR and the molecular chaperone HSP70, thereby protecting AR proteins from ubiquitin-proteasome-mediated degradation. Collectively, these findings provide a molecular basis for the adverse clinical outcomes observed in smokers, suggesting that the accumulation of cotinine may serve as a potential risk factor for prostate cancer progression and treatment resistance. - Source: PubMed
Publication date: 2026/08/19
Hayashi RiriKudo YudaiYoshino YutaShiota MasakiFujimoto NaohiroIkari AkiraEndo Satoshi