KDM3A (Lysine Demethylase 3A)

Consistently, pharmacological agents-Trichostatin A as a histone deacetylase inhibitor and chaetocin as a histone methyltransferase inhibitor-induced nucleosome scattering and converted U2OS cells into iTS cells, whose conditioned media exerted tumor-suppressive effects. Our findings highlight nucleosome clustering as a key epigenetic feature responsive to both biophysical and chemical cues, underscoring its role in microscale chromatin remodeling and reprogramming of the tumor microenvironment.

H3K9me3 loss per se phenocopies Lamin A/C inactivation, reducing PAR levels and deregulating fork restart by RECQ1. Hence, nucleoplasmic Lamin A/C, H3K9me3 and PARylation levels are crucial, mechanistically linked modulators of fork dynamics upon mild RS, with important implications for chemotherapy response and for Lamin A/C dysfunction in human disease.

Instead, we observed site-specific changes driven by altered expression of methyltransferases and demethylases, particularly decreased KMT1F (H3K9 methylation) and KMT2B (H3K4 methylation) and increased KDM2A (H3K36 demethylation), KDM3A (H3K9 demethylation), and KMT5A/SETD8 (H4K20 monomethylation). These findings reveal that the histone methylation landscape under hypoxia is governed by a compensatory interplay between one-carbon metabolism and chromatin-modifying enzyme regulation.

Clinical analyses revealed elevated KDM3A expression in metastatic NSCLC tissues, with a negative correlation between KDM3A and H3K9me2, and a positive association between KDM3A and FOXP3. These findings establish KDM3A as an epigenetic modulator of NSCLC progression through H3K9me2-dependent regulation of EMT and metastatic pathways, highlighting its therapeutic potential for NSCLC treatment.

Both in vivo and in vitro experiments demonstrated that mPEG-NH2/2-FPBA/TubA effectively delivered TubA, resulting in a significant reduction in tumor growth; decreased expression of KDM3A, HIF1A, and Ki67; and an increase in H3K9me2 levels. This study presents an effective material delivery strategy for lactylated proteomic nanoparticles and elucidated their mechanism of action.

Protein phosphorylation levels of AKT, ERK1/2, and HER2 were also reduced. These results indicate that KDM3A contributes to TRA resistance in HER2+BC cells via the PI3K/AKT/ERK pathway, suggesting its potential as a therapeutic target for overcoming TRA resistance in HER2+BC.

Then, Weighted Gene Co-expression Network Analysis (WGCNA) combined with Least Absolute Shrinkage and Selection Operator (LASSO) analysis was used to obtain key genes associated with OA diagnosis, including BCL6 co-repressor (BCOR), Coiled-Coil Domain Containing 59 (CCDC59), Jun Proto-Oncogene (JUN), Lysine Demethylase 3A (KDM3A), L3MBTL Histone Methyl-Lysine Binding Protein 4 (L3MBTL4) and Zinc Finger Protein 292 (ZNF292). Finally, the role of KDM3A in OA cell model was verified by constructing KDM3A overexpression and silencing cell lines.ResultsIt was found that overexpression of KDM3A significantly downregulated β-catenin expression compared with the oe-NC group, thus affecting a series of biological processes in the OA cell model, specifically, increasing antioxidant capacity, reducing levels of inflammatory factors, and inhibiting extracellular matrix degradation.ConclusionThis study not only provided six key target genes for OA but also revealed the important role of KDM3A in OA, providing a reference for gene targeted therapy for OA patients.

ZSH-512 efficiently inhibited tumorigenesis in CRC-patient-derived tumor xenografts (PDXs) with high KDM3A expression, suggesting KDM3A as a potential predictive biomarker. Collectively, ZSH-512 is a promising therapeutic candidate for targeting CRC-CSCs with high efficacy.

Furthermore, we show in bladder injected-liver metastasis xenograft model that USP13 inhibits bladder cancer metastasis through destabilizing cytoplasmic KDM3A. Collectively, our findings identify KDM3A is an important regulator of bladder cancer cell growth and metastasis and targeting USP13/KDM3A complex could be a valuable strategy to ameliorate bladder cancer progression and metastasis.

Drug screening identified therapeutic candidates, including Tazemetostat for EZH2 and lithium compounds for GSK3β, underscoring their potential for targeted treatment. These findings provide novel insights into the complexity of HCC pathogenesis, suggesting that the identified hub genes could serve as diagnostic or prognostic biomarkers and therapeutic targets. While bioinformatics-driven, this study offers a strong basis for future clinical validation to advance precision medicine in HCC.

PPA/HG promotes the infiltration and activation of effector T lymphocytes, meanwhile decreasing the population of immunosuppressive regulatory T cells. Systemic administration of PPA/HG significantly inhibits the progression of orthotopic triple-negative breast cancer and pancreatic ductal adenocarcinoma with minimal side effects.