LDHB (L-lactate dehydrogenase B chain)

The glycolysis-CCNB2-H3K18la-TTK/BUB1B signaling axis exacerbates the malignant progression of PDAC, providing insights into potential lactylation-based therapeutic strategies for this disease.

This study identifies m6A-related SNPs as important regulatory factors shared between OC and EM. By integrating genetic, transcriptomic, and functional data, we highlight immune and metabolic pathways-especially those involving LDHB, IFITM2, and HLA-DQB1-as key contributors to cisplatin resistance. These findings provide potential therapeutic targets and a framework for understanding m6A-associated mechanisms in ovarian cancer progression. Further in vivo studies are needed to validate the direct effects of specific m6A-SNPs.

The levels of β‑catenin mRNA and H3K18 lactylation were also found to be elevated in IH tissues. Taken together, the results of the present study revealed that lncRNA NEAT1, which is upregulated in hemangioma, binds with and stabilizes LDHB, subsequently elevates the levels of cellular lactate and H3K18 lactylation, potentiates β‑catenin transcription and ultimately enhances the proliferation of hemangioma cells.

In addition, we conducted pathway enrichment analyses to elucidate the mechanisms underlying drug resistance for paclitaxel, 5-fluorouracil (5-FU), gemcitabine, and cetuximab. Importantly, our findings are consistent with prior experimental studies, providing literature-based validation of our results. Overall, our DNN-based TL approach achieved strong predictive performance across PDX & TCGA datasets and enrichment analyses provided valuable biological insights into drug resistance mechanisms.

Furthermore, reported LDH allosteric inhibitors, including cGmC9 and fluoxetine, preferentially inhibited LDHBtr compared to the native LDHB, by preventing tetramer formation. Overall, this work highlights the central role of tetramerization in regulating LDH activity, and the therapeutic potential of targeting this process. It also establishes LDHBtr as a valuable tool for screening tetramerization disruptors, paving the way for next-generation LDH inhibitors to target cancer metabolism.

This study provides the first comprehensive inhibition profile of R. crenulata targeting LDH isoenzymes. It underscores the potential of R. crenulata in LDH-targeted therapeutics and supports its further development for cancer treatment.

This model not only advances our understanding of cancer metabolism but also suggests novel strategies for biomarker development, metabolic imaging, and targeted therapies. By reframing lactate as a central determinant of oncologic remodeling, the CILLO hypothesis provides a foundation for translational advances in oncology and personalized medicine.

We also introduced ArGO-LDHA-1, a covalent inhibitor targeting LDHA's hyperreactive arginine residues, showing potential to enhance chemotherapy efficacy. This work highlights the biological significance of arginine residues and provides a platform for large-scale profiling of arginine reactivity.

Integrated analysis of differentially expressed genes (DEGs) and differentially abundant metabolites (DAMs) demonstrated that MPA significantly alters the metabolism of key compounds (GMP, phenol, glutathione, NAD+, cytosine) and regulates critical genes (tyrosine, LDHA, LDHB). Notably, the dysregulation of genes and metabolites associated with reactive oxygen species (ROS)-related pathways may serve as a central mechanism by which MPA facilitates ferroptosis and apoptosis in bladder cancer.

Drug analyses suggested cisplatin and sunitinib downregulated oncogenic targets. Silencing ABCB1 or AKR1C3, or overexpressing LDHB, suppressed KIRC cell proliferation and migration in vitro; LDHB overexpression combined with sorafenib significantly reduced tumor growth in vivo. We propose a robust immunometabolism-based diagnostic model and six experimentally supported biomarkers for KIRC, providing mechanistic insight into tumor-immune interactions and potential avenues for personalized therapy.

Our findings reveal a tumor-specific mechanism in which CDK1 reprograms LDH isoenzyme composition to direct lactate toward NADH production, ensuring energy homeostasis during mitosis. This underscores the therapeutic necessity of targeting both LDHA and LDHB in cancer.

The risk score developed in this study demonstrates excellent robustness and is capable of effectively predicting the prognosis of LSCC patients. Our study holds promise for advancing both prognostic prediction and therapeutic intervention in LSCC management.