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

Inhibition of EZH2 with either DZNep or EPZ6438, EZH2 inhibitors, or siRNA significantly decreased the proliferative and metastatic capacity of NSCLC cells induced by nicotine treatment...Furthermore, the c-Myc inhibitor 10058-F4 exhibited synergistic effects with the EZH2 inhibitor DZNep in suppressing NSCLC cell proliferation and metastasis both in vitro and in vivo.Nicotine regulates the c-Myc/EZH2 signaling pathway via OTUB1-mediated deubiquitination, thereby promoting the proliferation and metastasis of NSCLC cells. This research reveals novel molecular mechanisms of nicotine in the development of NSCLC, providing a theoretical foundation for future therapeutic strategies.

Nevertheless, the elevated expression of EZH2 we have observed in our findings could be utilized as a pretherapeutic assessment prior to targeted therapies with tazemetostat. Subsequent research should substantiate this hypothesis.

Therefore, the present review focuses on the multifaceted functions of EZH2 and its pathophysiological mechanisms in tumor proliferation, with a specific emphasis on endocrine tumors. Investigating EZH2 mechanisms and targeting with inhibitors and drugs is an active area of research that could offer a promising avenue for treatment and a better understanding of molecular therapeutic interventions.

JNSF may attenuate HUA-induced renal injury by inhibiting apoptosis through the downregulation of ROS/HIF-1α/EZH2 pathway.

Proportions were calculated from the samples in clinical trials supporting FDA-approval and FAERS, respectively. In this investigation, contemporary FDA-approved therapies for STS are associated with increased risk of AEs.

This study validates the prognostic value of the IMTCGS and identifies EZH2 as a novel prognostic biomarker in MTC patients. The therapeutic potential of EZH2 warrants further investigation in larger cohorts.

Thus exosomes are granted the ability to regulate numerous physiological functions and act as crucial messengers between cells by influencing gene expression in the recipient cell. We conducted this review to focus on EZH2's substantial biological role and the mechanisms that regulate it, driven by the desire to understand the possible impact of exosomal RNAs on EZH2 expression.

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.

Furthermore, our findings demonstrate that pharmacological inhibition of EZH2 leads to a significant upregulation of RB1 expression levels, mediated by enhanced enrichment of the activating histone marker H3K27ac at the RB1 enhancer region, as evidenced by ATAC-sequencing and ChIP-qPCR assays. These insights unveil a promising clinical avenue for combating RB1-mediated drug resistance in TNBC through the strategic integration of epigenetic-targeting agents.

report that inhibiting enhancer of zeste homolog 1 (EZH1) and EZH2 enhances chimeric antigen receptor (CAR)/T cell receptor (TCR)-based therapies by reprogramming tumors to be more immunogenic and improving T cell phenotype and demonstrate the efficacy of this combination in preclinical models across hematologic and solid cancers. Clinical trials are ongoing to evaluate its safety and therapeutic potential.

P1, N=64, Suspended, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Sep 2026 | Trial primary completion date: Mar 2025 --> Sep 2026

Inhibitors like MAK683 and EED226 disrupt EED's ability to maintain PRC2 activity, thereby reducing H3K27me3 levels and reactivating tumor suppressor genes. Valemetostat, a dual inhibitor of both EZH2 and EED, has shown promising results in aggressive cancers like diffuse large B-cell lymphoma and small-cell lung cancer, underlining the therapeutic potential of targeting multiple PRC2 components...Tazemetostat, a selective EZH2 inhibitor, has demonstrated significant clinical efficacy in EZH2-mutant cancers, such as non-Hodgkin lymphomas and epithelioid sarcoma. However, the compensatory function of enhancer of zeste homolog 1 (EZH1) in some cancers requires dual inhibition strategies, as seen with agents like UNC1999 and Tulmimetostat, which target both EZH1 and EZH2. Given PRC2's multifaceted role in cancer biology, its inhibition represents a promising avenue for therapeutic intervention. The continued development of PRC2 inhibitors and exploration of their use in combination with standard chemotherapy or immunotherapy has great potential for improving patient outcomes in cancers driven by PRC2 dysregulation.

Subsequently, we transfected cancer cells with nonenzymatically modified apoptin mRNAs by utilizing the three imidazole-activated guanosine derivatives compounds and monitored the induced apoptosis. These findings suggest that 2'O-Me-2-amino-IM-modified apoptin mRNA could serve as a promising tool for cancer therapy by inducing apoptosis while selectively modulating EZH2 expression, a key regulator in oncogene suppression.

In addition, specific pharmacological agents have been shown to modulate H3K27 methylation levels, thereby modulating inflammation and carcinogenesis. This review comprehensively summarises the current characteristics and clinical significance of epigenetic regulation of H3K27 methylation in the context of inflammatory response and tumor progression.

Additionally, Capsanthin was found to suppress the expression of epithelial-mesenchymal transition (EMT) markers in metastatic brain TNBC cells and mesenchymal stem cells. Our results suggest that Capsanthin can modulate the tumor microenvironment and inhibit key pathways involved in cancer progression, offering potential therapeutic benefits for patients with TNBC brain metastases.

In this review, drawing upon our comprehensive understanding of the factual underpinnings of EZH2's role in cancer, we aim to clarify the crucial importance of targeting EZH2 in cancer treatment. Furthermore, we summarize the current research landscape surrounding targeted EZH2 inhibitors and offer insights into potential future applications of these inhibitors.

We assessed PQQ's anti-tumor effects across various cell lines and found strong activity against B cell lymphoma cells with elevated EZH2 levels. Notably, PQQ is a naturally occurring compound with antioxidant and neuroprotective properties, approved as a dietary supplement in the U.S. This study highlights that PQQ, used as a dietary supplement, inhibits PRC2 methyltransferase activity, offering new insights for targeted anti-lymphoma therapies.

The downregulation of EZH2 can potentially enhance the efficacy of immune checkpoint inhibitors in patients with TNBC and may provide a new therapeutic strategy.

These findings highlight EZH2 as a critical regulator of astrocyte function, with its disruption contributing to neurodevelopmental disorders. This study provides novel insights into the molecular pathways governing astrocyte differentiation and suggests EZH2 as a promising therapeutic target for gliomas and other CNS disorders.

A striking number of progression-associated mutations occurred in chromatin methylation modifiers, including EZH2, suggesting that EZH1/2 inhibition may also benefit patients with CTCL. Knowledge of these molecular changes should be leveraged for improved disease monitoring, biomarker-informed clinical trial design, and new therapeutic strategies in this challenging and incurable cancer.

In an orthotopic xenograft HCC mouse model, ASO treatment repressed tumor growth, improved tissue phenotype, and extended the median survival. Our data highlight therapeutic potential of the lead exon-skipping ASO in treating HCC.

PTEN presence, BCL2 mutations, and low or undetectable baseline IL-2 levels were associated with improved patient survival following treatment with C + R, supporting a potential role for these biomarkers in guiding treatment selection for patients with indolent non-Hodgkin lymphoma.

EZH2-targeted therapies have been successfully used to treat patients with follicular lymphoma and epithelioid sarcoma, but their clinical use in melanoma has not been described. Here, we describe a pediatric patient with multiply relapsed melanoma harboring an EZH2 A692V missense mutation, treated adjuvantly with the EZH2 inhibitor tazemetostat, who experienced a prolonged relapse-free survival.

In human B cell lymphoma, EZH2 inhibition (tazemetostat) improved the efficacy of anti-CD19 CAR-T by enhancing activation, expansion, and tumor infiltration. Lastly, combined EZH1/EZH2 inhibition (valemetostat) further boosted CAR-T efficacy and expansion in multiple cancers. This study shows that EZH1/2 inhibition reprograms tumors to a more immunogenic state and potentiates ACT in preclinical models of both liquid and solid cancers.

However, Staphylococcus aureus Cas9 (SaCas9) gave a variant correction (52.5%) that was not significantly different than SpCas9, and encouragingly the lowest alteration of the nonvariant allele (2.0%). Thus, the therapeutic strategy using the small SaCas9 enzyme, a size that allows flexibility in therapeutic delivery, was the most optimal for targeting the Weaver syndrome EZH2 variant c.2035C>T p.Arg684Cys.

NOTCH1 signaling influences DLBCL development and myocardial infarction severity through the EZH2/STAT3 pathway, leading to increased heart fibrosis.

The SMYD2-EZH2 expressions and c-MET activation were notably suppressed by OC treatments in vitro and in collected animal primary tumors. OC and olive phenolics are potential nutraceutical interventions useful for CRC control and the prevention of its relapse.

Knocking down MCM complex genes reduced hTERT expression, inducing HCC cell senescence and enhancing the therapeutic efficacy of sorafenib. These findings suggest that the EZH2/MCM complex/hTERT axis could serve as a novel therapeutic target for HCC.

Loss of EZH2 did reduce recruitment of inflammatory cells and, when combined with a more aggressive PDAC model, promoted widespread PDAC progression and remodeling of the tumor microenvironment. This study suggests that expression of EZH2 in adult acinar cells restricts PDAC initiation and progression by affecting both the tumor microenvironment and acinar cell differentiation.

In conclusion, GGCT silencing restrained the proliferation and metastasis, and promoted apoptotic levels of HCC cells via regulating PTEN/PI3K/AKT pathway-mediated glycolysis, which might offer a prospective candidate in treating HCC.

Our study uncovers the importance of T cell EZH2 in human and mouse atherosclerosis. Inhibition of Ezh2 in CD4+ T cells drives type 2 immune responses, resulting in an accumulation of iNKT2 and Th2 cells, memory T cells and anti-inflammatory macrophages that limit the progression of atherosclerosis.

The findings demonstrated a strong link between the radiomics model, EZH2 expression, and patient prognosis. This noninvasive approach provides valuable insights into the therapeutic management of HCC.

LncRNA UCA1 overexpression or p27 downregulation reduced the protective effect of KLF9 downregulation on cardiomyocyte hypertrophy. In conclusion, KLF9 activates lncRNA UCA1 expression, and lncRNA UCA1 epigenetically suppresses p27 expression, thereby exacerbating cardiomyocyte hypertrophy in HOCM.

Importantly, EZH2 inhibitors effectively treat myeloma-induced osteolytic lesions. Thus, targeting EZH2 represents a potential therapeutic strategy for preventing and managing myeloma bone disease.

Gene expression levels of KRT-14 and EZH2 were significantly (P ≤ 0.05) upregulated in PSO treated group as compared to positive control group. Histopathology revealed that pumpkin seed oil preserved the structural integrity of colon.

Mechanistically, EZH2's alternative splicing was mediated by splicing factor SNRPB. In summary, this study revealed that alternative splicing of EZH2 regulates HCC.

Bax and P21 protein levels were significantly upregulated following DNC treatment, whereas Bcl-2 and P53 protein levels were downregulated in DNC-treated breast cancer cells. In summary, dendrosomal nanocurcumin demonstrated potent anti-tumor effects against breast cancer cells, suggesting its potential as a therapeutic agent in breast cancer treatment.

While PROTAC-mediated degradation of EZH1-PRC2 in quiescent cells does not reduce H3K27me3, it partially displaces cPRC1. Our results reveal an evolutionarily conserved switch to less catalytically active Polycomb complexes in non-dividing cells and raise concerns about using PRC2 inhibitors in cancers with significant populations of non-dividing cells.

Results highlighted that the EZH2 expression was correlated with immune-related pathways, infiltration of various immune cells, immune score, the expression of immune checkpoints and immunotherapy sensitivity. Collectively, we suggested that EZH2 might be considered as predictor on the therapeutic effects of ICBs on UM patients, and a potential target for combined immunotherapy.

Lastly, 5-Aza-CdR regulated miR-155-5p expression by modulating its promoter methylation and influenced the malignant behavior of PCa cells. EZH2 promotes H3K27me3 methylation, repressing miR-155-5p expression, which subsequently upregulates the downstream targets SMAD2 and TAB2 and promotes PCa cell proliferation, epithelial-mesenchymal transition (EMT), migration and invasion.

Quercetin, the effective component of XYSJD, promoted apoptosis of TNBC cells via blockade of the EZH2/AKT1 signaling pathway. These findings aim to provide a more reliable basis for the clinical application of XYSJD in the treatment of TNBC.

Loss of EZH2 did reduce recruitment of inflammatory cells and, when combined with a more aggressive PDAC model, promoted widespread PDAC progression and remodeling of the tumor microenvironment. This study suggests expression of EZH2 in adult acinar cells restricts PDAC initiation and progression by affecting both the tumour microenvironment and acinar cell differentiation.