ZMYND8 (Zinc Finger MYND-Type Containing 8)

The resulting OTUD4-ZMYND8-DDX3X signaling axis drives canonical WNT/β-catenin signaling, upregulates CSF1 expression and promotes M2 polarization of macrophages, collectively fostering invasive behavior and establishing an immunosuppressive niche conducive to spinal metastasis. Collectively, these findings establish the OTUD4-ZMYND8-DDX3X axis as a pivotal regulator of spinal metastasis in TNBC and highlight its potential as a therapeutic target for inhibiting metastatic progression.

Using CRISPR-based genome-wide perturbation screens, we investigated the genetic dependencies of venetoclax and the BCL2/BCL2L1 dual inhibitor AZD4320. Accordingly, in AML patient samples we found reduced expression of the respective m6a or NuRD complexes was significantly associated with monocytic differentiation and ex vivo resistance to the same drugs. These findings provide critical insights into previously undescribed mechanisms of BCL2 family inhibitor resistance in AML.

These results highlight ZMYND8 as a key player in hypoxia-induced metabolic reprogramming of breast cancer cells and provide new insights into the epigenetic regulation of cancer metabolism. Our study unveils a novel mechanism linking epigenetics, metabolism, and immune evasion in breast cancer, opening new avenues for targeted therapeutic interventions aimed at disrupting this axis.

ZMYND8 was identified as a key downstream mRNA target (AUC = 0.811), and three potential therapeutic drugs-demecolcine, piroxicam, and vorinostat-were predicted based on DSigDB screening and validated by molecular docking, with binding energies of -6.48, -7.15, and -5.39 kcal/mol, respectively. Finally, in vitro cellular assays confirmed that SNHG25 expression was elevated in COAD cell lines (p < 0.0001), and its knockdown significantly suppressed cell proliferation, migration, and invasion. This study highlights that SNHG25 is highly expressed in COAD and promotes tumor progression through multiple mechanisms, advancing research and treatment strategies for this malignancy.

This model identifies mutated genes that are associated with the most aggressive ATCs and thus may aid in preoperative risk assessment when evaluating patients for surgery for curative intent.

Moreover, in vivo studies revealed that overexpression of ZMYND8 resulted in accelerated tumour growth in PC xenografts, which was reversible through the knockdown of c-Myc or treatment with 2-deoxy-D-glucose. Collectively, our data suggest that ZMYND8 functions as a critical metabolic regulator in PC cells by tightly regulating c-Myc activity and may represent a promising novel therapeutic target for advanced pancreatic cancer treatment.

Despite chemotherapy with carboplatin-paclitaxel followed by a second-line regimen, rapid disease progression ensued, leading to pleural effusion, cardiac tamponade, and fatal cardiac arrest within 2 months. BSQCC is an aggressive carcinoma requiring prompt diagnosis and treatment. This case underscores the importance of heightened awareness, molecular profiling, and further research to improve outcomes in rare lung cancers.

Furthermore, ZMYND8 upregulation increases the sensitivity of MM cells to carfilzomib. Taken together, these findings demonstrate that ZMYND8 epigenetically activates CEBPE transcription and suppresses MM cell growth by inhibiting the adaptive UPR, suggesting that ZMYND8 can be a novel therapeutic target for patients with MM.

Histone reader ZMYND8 specifically confers resistance to cancer cells against trastuzumab and/or pertuzumab. Targeting c-Myc or cPLA2α effectively overcomes anti-HER2 therapy resistance in patient-derived xenografts. Collectively, this study uncovers a druggable signaling cascade that drives resistance to HER2-targeted therapies in HER2+ breast cancer.

Indisulam is a promising therapeutic candidate for AMKL and the RBM39-mediated ZMYND8 splicing plays an important role in promoting the development of AMKL.

These findings reveal the critical role of ZMYND8-dependent epigenetic programming induced by androgen deprivation therapy in orchestrating lineage fate. Targeting ZMYND8 emerges as a promising strategy for impeding NEPC development.

Notably, we identify a therapeutic vulnerability in TNBC cells whereby combination treatment with ABL allosteric inhibitors and EZH2 inhibitors elicits a synergistic decrease in TNBC cell survival in vitro, and impairs TNBC metastasis, prolonging survival of tumor-bearing mice treated with the combination therapy. ABL Kinases indirectly impact EZH2 catalytic activity by blocking a signaling cascade that leads to changes in the phosphorylation, protein interactions, and function of the PRC2 catalytic component EZH2 in TNBC.