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

This review aims to enhance the current understanding of EZH2 and its roles in the TME, cancer development, and therapeutic responses. This review will discuss the canonical and non-canonical functions of EZH2, summarize its established and evolving roles in cancer and the TME, and highlight its effects on tumor immunity and therapeutic efficacy.

Our results suggest that EZH2 may play a functional role in the maintenance and progression of at least a subset of canine T-cell lymphoma and may represent a potential driver of tumor malignancy. These findings contribute to a deeper understanding of lymphomagenesis and support the potential of EZH2 as a therapeutic target in canine T-cell lymphoma.

Notably, Napabucasin effectively inhibited ovarian cancer metastasis in vivo. Collectively, our findings elucidate a previously unrecognized mechanism by which EZH2 governs metastatic progression through cholesterol metabolic rewiring and propose Napabucasin as a promising therapeutic strategy for ovarian cancer, particularly in tumors with EZH2 hyperactivation.

PcG complex genes are broadly dysregulated in PDAC. SUZ12 upregulation marks an epithelial state characterized by acinar identity loss, proliferative remodeling, and PRC2-MHC-I co-expression, supported by prior protein-level and functional data. Germline genetic analyses were negative or underpowered, and direct mechanistic validation remains needed.

In vitro cellular experiments showed that the knockdown of DDX11-AS1, CDC25A, and HELLS inhibited cell proliferation and invasion by promoting ferroptosis in Huh7 cells. The 11 ferroptosis-related genes and DDX11-AS1 may serve as valuable prognostic biomarkers and potential immunotherapeutic targets in HCC.

The combined treatment of syngeneic LLC lung cancer with C36 and a PD-1 antibody significantly enhances anti-tumor efficacy. Our study identifies a new allosteric mechanism of PRC2 inhibition and paves the way for the development of highly selective EZH2/PRC2 inhibitors for combination therapy.

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.