ALDH3A1 (Aldehyde Dehydrogenase 3 Family Member A1)

Anemarrhenone A (AA), with IC50 values of 5.19 ± 1.25 μM for Hep3B cells and 4.02 ± 1.13 μM for HepG2 cells, exhibited anti-HCC activity comparable to that of sorafenib (IC50 of 5.63 ± 0.27 μM for Hep3B cells and 2.34 ± 0.28 μM for HepG2 cells). ALDH3A1 emerged as a direct functional target through which AA exerted its anti-HCC activity. This research revealed a potential tumor suppressive pathway mediated by AA and provided a strategic approach against HCC.

This integrative single-cell and machine-learning study delineates the molecular heterogeneity of LM in ICC and identifies twelve feature genes linking LM with tumor aggressiveness. These findings provide novel insight into LM-driven oncogenic mechanisms and propose CYC1 and other LM-associated genes as potential biomarkers and therapeutic targets for ICC.

Key apoptosis-associated genes, including ALDH3A1, CYP1A1, NOS3, MT1X, and CES1, were further validated by RT-qPCR. These findings suggest CNDCM as a potential candidate for breast cancer therapy.

Our data further indicate that xenografting can induce significant cellular reprogramming. Comprehensive characterization of ovarian cancer cell-derived xenograft is therefore essential, as they represent a valuable translational platform for investigating therapy adapted ovarian cancer cells.

Notably, the key polyamine biosynthesis regulator AMD1 was downregulated in both M2 macrophages and dendritic cells in recurrent lesions, paralleling metabolic evidence of altered arginine-polyamine pathways. These findings suggest that recurrent CA involves coordinated metabolic dysregulation across keratinocytes and immune cells, highlighting potential targets for immunometabolic intervention.

Critically, ALDH3A1 elevation selectively curbs EBV-positive tumor growth, exploiting an infection-specific vulnerability in redox signaling. Thus, our findings integrate EBV-driven redox remodeling with Wnt/β-catenin signaling activation and propose ALDH3A1 induction as a promising therapeutic strategy for EBV-associated carcinomas.

Hyperproliferative spheroids (HRPS) showed increased proliferation and tumorigenic potential, whereas hypoproliferative spheroids (HOPS) demonstrated enhanced migration and resistance to cisplatin and radiation...Notably, the gene expression profiles of Cluster 3 in the HOPS and Cluster 1 in the HRPS closely matched the expression patterns observed in the HNSCC-TCGA dataset. These clusters also displayed a high transcriptional correlation between patient tumors and their xenografts, reinforcing the clonal nature of HNSCC's genetic and functional diversity of HNSCC.

RNA-seq further identified aldehyde dehydrogenase 3A1 (ALDH3A1) as potentially downstream target of GOT1. These findings suggest that GOT1 knockdown may improve clinical outcomes in HNSCC.

The RRMG signature predicts radioimmunotherapy outcomes for patient stratification. Identifying ouabain and novel compounds highlights targeting metabolic vulnerabilities as a translatable strategy to overcome resistance.

This work shows that ADH5 and ALDH3-family enzymes function as tier 1 defense mechanisms against endogenous DNA-damaging metabolites in keratinocytes. Enhanced detoxification of endogenous aldehydes might prevent DNA damage and mutagenesis, which drive Fanconi anemia-associated head and neck and other mucosal squamous cell carcinomas.

Drug sensitivity analysis revealed GW.441756, imatinib, and WH.4.023 were more effective in the low-risk group, with varying sensitivities to other drugs in the high-risk group. The qRT-PCR, WB, and IHC results matched the bioinformatics analysis, showing upregulated ATP7B expression in BRCA, indicating the high prognostic potential of the identified genes. ADME-related prognostic genes (GSTM2, ADHFE1, ALDH2, NOS1, ATP7B, and ALDH3A1) are implicated in BRCA pathogenesis, suggesting new therapeutic strategies for BRCA treatment.

In vivo studies confirmed that this axis effectively inhibits tumor growth without apparent toxicity, and SR8278 also shows a synergistic effect when used in combination with melatonin. Our findings elucidate the role of the "melatonin-BMAL1-ALDH3A1" axis in combating breast cancer, offering a new direction for treatment and laying the groundwork for developing precision chronotherapy-based combination regimens.