HDAC5 (Histone Deacetylase 5)

These findings uncover a previously unrecognized CK2-HDAC5-Ku70 signaling axis that governs DNA repair pathway choice by regulating DNA end resection. Targeting this axis provides a mechanistic rationale for enhancing PARP inhibitor sensitivity in PDAC, including tumors without classical homologous recombination deficiency.

Our study reveals HDAC5/H3K27ac/KPNA2 axis as the anti-metastatic mechanism of TBMS1 in cervical cancer, suggesting TBMS1 serves as a promising drug for cervical cancer treatment.

Additionally, a higher throughput thermal shift format was developed using dot blot analysis. Thermal shift analysis offers a useful complement to enzyme activity assays for characterization of HDAC inhibitors.

Notably, TNF-α downregulated HDAC5 by promoting WTAP-mediated m6A modification of HDAC5 mRNAs, which are subsequently regulated by YTHDF2 to reduce mRNA stability. Our results reveal a synergistic epigenetic regulatory mechanism between SEs and m6A modification of MSC immunosuppressive functions and provide a novel strategy to promote the clinical therapeutic potential of MSC infusion in inflammatory diseases.

The CBX4-HDAC5-CERS6 axis influences AML malignant progression by regulating sphingolipid metabolism, and targeted intervention of this axis may represent a novel therapeutic strategy for AML.

Our data further demonstrated that pharmacological or genetic inhibition of c-Myc effectively reversed the resistance phenotype mediated by HDAC5 loss, suggesting a therapeutic strategy centered on "KRAS-MYC dual-node blockade." Furthermore, the expression levels of HDAC5 and the acetylation status of c-Myc may serve as potential biomarkers for predicting the therapeutic response to MRTX1133. These findings provide insights into overcoming resistance to KRASG12D inhibitors and offer potential biomarkers and combinatorial therapeutic strategies for precision treatment of PDAC.

Cytoplasmic HDAC6 increases self-renewal and cell migration, compared with nuclear HDAC6 enhancing EWSR1-FLI1 transcription. Thus, the diverse expression and roles of HDACs in sarcoma pathogenesis will be a solid foundation to guide personalized therapeutic application of HDAC modulators in sarcomas.

Furthermore, patient profiling based on the epigenetic state of the super-enhancers controlled by HDAC4 successfully identified a priori CRC patients resistant to platinum. This study supports HDAC4 as a key mediator of oxaliplatin resistance in FBXW7-mutated CRC and highlights the remodeling of a well-defined super-enhancer repertoire as part of the process of OXPT resensitization.

Lactate-driven MRE11 Lys673 lactylation mediates radioresistance, while SSD reverses this via HIF1α/HDAC5 axis activation. Our findings identify SSD as a radiosensitizer and HDAC5/MRE11 as potential therapeutic targets for TNBC.

Our findings reveal that KAT2B suppresses de novo lipogenesis by interfering with HDAC5-LSD1 complex assembly, and highlight the potential of FASN inhibitors as a therapeutic strategy for RCC patients with low KAT2B expression.

This study reveals a previously unrecognized anti-TNBC mechanism of CCT196969 through the HDAC5/RXRA/ASNS axis. This provides potential candidate targets for the treatment of TNBC and a theoretical basis for the clinical treatment of TNBC patients with CCT196969.

Importantly, the tumor-suppressive effect of DHX9 knockdown was reversed by BECN1 downregulation. In conclusion, the previously unrecognized significance of DHX9 in mediating the epigenetic silencing of BECN1, which is essential for autophagy and tumorigenesis, highlights its potential as an effective biomarker as well as a prospective therapeutic candidate for BC.