EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)

In silico knockout analysis demonstrated that these five model genes played critical roles in metabolic reprogramming, cell cycle regulation, and extracellular matrix modulation. By integrating multi-algorithm diagnostic modeling with in silico gene knockout analysis, this study systematically identified key FRGs and regulatory networks in GC.

MiR-25-3p was downregulated in SAA patients and regulated CD4+ T cell activation and proliferation by targeting EZH2. These findings provide novel insights into potential therapeutic targets for AA.

MHC Class II blockade lowered the ability of bone marrow to boost tumor growth, and reduced the ability of valemetostat with anti-PD1 to reduce tumoroid growth. Patient samples revealed a strong negative correlation between EZH2 and MHC Class II, suggesting that targeting EZH2 activity could lead to marked increase in MHC Class II and improve treatment responses in lung squamous cell carcinomas.

Mouse embryonic stem cells (mESCs) derived from protein kinase C inhibition (PKCi) exhibit self-renewal and pluripotency comparable to those ESCs captured by the classical 2iL (CHIR99021, PD0325901, and leukemia inhibitory factor) system...Thus, EZH2, a core subunit of PRC2, exhibits the distinct regulatory functions orchestrating mESCs at a poised state between self-renewal and differentiation under PKC inhibition. EZH2 exerts histone H3 methyltransferase activity to regulate Nanog expression as one of its key targets, thereby modulating the transcriptional regulatory network that maintains pluripotency and lineage specification in mESCs.

Enhancer of zeste homologue 2 overexpression was noted in cutaneous squamous cell carcinoma cases, indicating that enhancer of zeste homologue 2 had a potential role in cutaneous squamous cell carcinoma tumourigenesis.

EZH2 and PI3K pathway inhibitors achieve this by respectively inhibiting two key regulators of metabolism, MYC and HIF-1A, while concomitantly derepressing a pro-apoptotic stress sensor. Together, these studies reveal a promising therapeutic strategy for CRPC and demonstrate how metabolic plasticity can be fatally impaired by co-targeting upstream oncogenic nodes that converge on this important process.

For nearly twenty years, platinum-pemetrexed chemotherapy has persisted as the unchanged standard treatment; although recent progress in immunotherapy has modestly disrupted this therapeutic plateau, survival outcomes remain disappointingly limited...Preclinical and early clinical data demonstrate that EZH2 inhibitors-including tazemetostat, valemetostat, GSK126, EPZ011989, tulmimetostat, and novel PROTAC-based degraders such as MS1943-can suppress tumor progression, modulate the tumor immune microenvironment, and restore therapeutic sensitivity...Further understanding the dual canonical and non-canonical roles of EZH2 in tumor biology will be key to optimizing targeted and combinatorial treatment strategies. Future research should focus on translating EZH2 inhibition into clinical benefit, identifying predictive biomarkers of response, and exploring rational combinations with chemotherapy, targeted drugs, or immunotherapy to improve survival outcomes in mesothelioma patients.

RNA sequencing revealed that Ezh2-deficient effector CD8+ T cells exhibit the increased expression of terminal differentiation-related molecules and apoptosis-related genes. These results demonstrate that Ezh2 functions downstream of menin and is essential for the proper regulation of T cell-dependent antitumor immunity.

Overall, crebanine effectively suppresses HCC tumor growth and progression via modulation of the EZH2/DUSP1/Akt signaling pathway. Crebanine shows potential as a promising therapeutic agent for HCC treatment.

DOX-resistant breast cancer cell models were established and treated with the EZH2 inhibitors tazemetostat or GSK126, alone or in combination with DOX. EZH2 is a critical determinant of DOX resistance in breast cancer by sustaining DNA damage tolerance and metabolic homeostasis. Pharmacological targeting of EZH2 in combination with DOX represents a rational strategy to overcome chemoresistance in breast cancer.

Pharmacological inhibitors of EZH2, including tazemetostat, have shown promise in preclinical melanoma models by restoring antigen presentation, enhancing CD8+ T-cell infiltration, and reversing transcriptional programs associated with immune resistance. This review aims to summarize the role of EZH2 in the molecular pathogenesis of ALM, emphasizing its contributions to epigenetic regulation, tumor plasticity, and immune escape, and discusses emerging therapeutic strategies targeting EZH2-mediated pathways to improve outcomes for this aggressive melanoma subtype.

Valemetostat, which inhibits EZH1/2, as well as tazemetostat in combination with other drugs have been subject of recent research. The purpose of this article is to review the role of EZH2 in normal B cell differentiation and in the pathogenesis of B-Cell lymphomas.