ezh2 inhibitors  (TargetMol)

Journal: Scientific Reports

Article Title: Investigating the oncogenic role of aberrant EZH2 in hepatoblastoma

doi: 10.1038/s41598-026-38038-0

Figure Lengend Snippet: Tumors with embryonal histology have features of cycling Hep T cell cluster. a . EZH2 is elevated in HB tumor though to varying degree based on histologic subtype. PRC2 components, SUZ12 and EED are often upregulated compared to normal adjacent liver, but protein expression patterns are not consistent. b . Gene expression was analyzed in tumor grouped by histologic subtype to look at PRC2 genes, tumor markers, and genes regulated by EZH2. EZH2 gene expression is highest in embryonal subtypes, as well as AURKB, Ki67, and GPC3. Fetal histology had the highest level of SUZ12 and CTNNB1 expression, where EED gene expression did not show elevation by subtype. Tumors with mixed epithelial histology had muted expression levels making interpretation difficult. (N = 33 liver, N = 25 tumor stratified by histology).

Article Snippet: In vitro cells were treated with EZH2 inhibitors (tazemetostat (EPZ-6438) 10 μM -Selleck, GSK126 5 μM, Tocris) for 72 h. Cisplatin (0-400 μM) was then administered for 24 h. HepG2 (RRID:CVCL_0027) cells (passage 5–25) were purchased from ATCC and not authenticated.

Techniques: Expressing, Gene Expression

Journal: Scientific Reports

Article Title: Investigating the oncogenic role of aberrant EZH2 in hepatoblastoma

doi: 10.1038/s41598-026-38038-0

Figure Lengend Snippet: Complex regulation through canonical and noncanonical mechanisms. a . Gene expression analysis of paired liver and HB tumor samples demonstrated upregulation of EZH2, AURKB, CTNNB1, and TGFβ. EED and SUZ12 are also upregulated though not significantly. MYC, CCND1, STAT3, and CDH1 are downregulated in tumor compared to liver. b . EZH2 protein expression in tumor is not in stoichiometric relationship with other PRC2 components. EZH2 and EED are observed in the nucleus. EZH2 expression is also observed in mitotic cells from HB tumor, where SUZ12 expression is highest in the cytoplasm. c . Paired patient liver and HB tumor gene expression was compared and demonstrated significant upregulation of EZH2 in HB. Slight upregulation was also seen in PRC2 components, SUZ12 and EED, with correlation between these genes in paired samples but inconsistent upregulation. d . EZH2 positive, mitotic cells are significantly increased in HB cells compared to normal human hepatocytes. This expression pattern is also elevated in HB patient derived cells compared to HepG2 cells, though not all HB cells show a statistical significance increase compared to HepG2.​(N = 22 pairs, paired patient tumor and liver).

Article Snippet: In vitro cells were treated with EZH2 inhibitors (tazemetostat (EPZ-6438) 10 μM -Selleck, GSK126 5 μM, Tocris) for 72 h. Cisplatin (0-400 μM) was then administered for 24 h. HepG2 (RRID:CVCL_0027) cells (passage 5–25) were purchased from ATCC and not authenticated.

Techniques: Gene Expression, Expressing, Derivative Assay

Journal: Scientific Reports

Article Title: Investigating the oncogenic role of aberrant EZH2 in hepatoblastoma

doi: 10.1038/s41598-026-38038-0

Figure Lengend Snippet: EZH2 inhibition makes HB cells more sensitive to Cisplatin treatment. a . Liver cancer cells treated with EZH2 inhibitors in vitro followed by cisplatin demonstrated differential response to treatment. HCN-NOS showed no response to EZH2 inhibitors alone (HBc108). HB cells, HUH6 and HBc130 showed improved response to cisplatin in combination with EZH2 inhibition, with variability between the inhibitors. HepG2 cells showed elevated cisplatin resistance but better response with EZH2 inhibition. HBc129 showed limited response to cisplatin and no added benefit of EZH2 inhibition, while HUH7, HCC cells showed better cisplatin response but no additive effect with EZH2 inhibitors. b . Cell morphology suggests improved cell death and synergy between EZH2 inhibitors and cisplatin treatment. (Images represent EZH2 inhibitors added for 24 h, then 400 μM cisplatin plus inhibitors for an additional 24 h – 20X images with trypan blue to highlight remaining dead cells.) (Cell lines represent 6 technical replicates, with biological triplicates for all experiments).

Article Snippet: In vitro cells were treated with EZH2 inhibitors (tazemetostat (EPZ-6438) 10 μM -Selleck, GSK126 5 μM, Tocris) for 72 h. Cisplatin (0-400 μM) was then administered for 24 h. HepG2 (RRID:CVCL_0027) cells (passage 5–25) were purchased from ATCC and not authenticated.

Techniques: Inhibition, In Vitro

Journal: Scientific Reports

Article Title: Investigating the oncogenic role of aberrant EZH2 in hepatoblastoma

doi: 10.1038/s41598-026-38038-0

Figure Lengend Snippet: EZH2 inhibition improves in vivo tumor response to cisplatin in HB PDX model. HB66 PDX model was pretreated with 150 mg/kg EPZ-6438 5 times per week. 5 mg/kg cisplatin was then started and EPZ-6438 continued to study termination. a . MRI images show tumor volume at initiation of treatment and at 2 weeks of treatment. b . Reduction of H3K27me 3 is shown following EPZ-6438 and cisplatin treatments alone, but enhanced, synergistic reduction is seen after combination treatment with EPZ-6438. c . When comparing tumor volume, cisplatin alone showed modest reduction in tumor growth, while EPZ-6438 and cisplatin plus EPZ-6438 showed even greater reduction in overall tumor growth, supportive of in vitro studies. (one PDX model, with biological duplicate or triplicate per condition).

Article Snippet: In vitro cells were treated with EZH2 inhibitors (tazemetostat (EPZ-6438) 10 μM -Selleck, GSK126 5 μM, Tocris) for 72 h. Cisplatin (0-400 μM) was then administered for 24 h. HepG2 (RRID:CVCL_0027) cells (passage 5–25) were purchased from ATCC and not authenticated.

Techniques: Inhibition, In Vivo, In Vitro

Journal: Scientific Reports

Article Title: Investigating the oncogenic role of aberrant EZH2 in hepatoblastoma

doi: 10.1038/s41598-026-38038-0

Figure Lengend Snippet: Qualitative next generation sequencing using CinCseq cancer panel to define genetic sequence variants. a . 11 patient tumors were sequenced from FFPE tissue to explore clinically relevant variants as well as VUS. EZH2 and SUZ12 have VUS in 11 out of 11 samples and EED in 9 out of 11. As expected, CTNNB1 variants are observed in 9 out of 11 patients. STAT3 variants are also observed but at a lower frequency. Other less frequently observed variants are also displayed. b . Schematic gene map drawings to represent the location of detected VUS in EZH2 and SUZ12 (all exons not shown).

Article Snippet: In vitro cells were treated with EZH2 inhibitors (tazemetostat (EPZ-6438) 10 μM -Selleck, GSK126 5 μM, Tocris) for 72 h. Cisplatin (0-400 μM) was then administered for 24 h. HepG2 (RRID:CVCL_0027) cells (passage 5–25) were purchased from ATCC and not authenticated.

Techniques: Next-Generation Sequencing, Sequencing

Journal: Frontiers in Immunology

Article Title: Integrative bulk and single-cell transcriptomics link EZH2 to immunosuppressive programs and tumor–Treg crosstalk in castration-resistant prostate cancer

doi: 10.3389/fimmu.2026.1725097

Figure Lengend Snippet: EZH2 is upregulated in PCa and associates with an immunosuppressive microenvironment and poor prognosis. (A) Study workflow integrating TCGA/GEO bulk datasets and single-cell analyses: immune-signature scoring, correlation with EZH2, derivation of EZH2-related IMDEGs, risk modeling and subtyping, cell-type–specific interrogation (malignant cells and Treg), cell–cell interaction profiling, and planned validation in EZH2-inhibitor–treated cell lines. (B) Paired tumor–normal comparison of EZH2 across TCGA cancers (Wilcoxon paired tests; *BH-adjusted P < 0.05, **BH-adjusted P < 0.01, ***BH-adjusted P < 0.001). Red and blue dots indicate tumor and matched normal samples, respectively. The red/blue panel background indicates whether EZH2 is upregulated or downregulated in tumors relative to matched normal tissues. PRAD is highlighted. (C) In TCGA-PRAD, EZH2 expression in lymph-node–positive tumors (N1) versus N0 tumors (Wilcoxon rank-sum test; BH-adjusted P = 2.42×10 -6 ; N0: n=393, N1: n=80). (D) Independent GEO cohort comparing EZH2 expression between HD-PCa and mCRPC (Wilcoxon rank-sum test; BH-adjusted P = 9×10 - ¹³; HD-PCa: n=22, mCRPC: n=29). (E) Kaplan–Meier analysis of PFI in TCGA-PRAD comparing EZH2-high (n=275) vs. EZH2-low (n=276) tumors (log-rank test; two-sided nominal P<0.0001). (F) Correlations between EZH2 and immune/stromal signatures in TCGA-PRAD. Enrichment scores for 29 curated signatures were calculated by ssGSEA and z-scored within cohort; associations with EZH2 were assessed by Spearman correlation, and only signatures with nominal P < 0.05 are shown. Asterisks denote significance (*P < 0.05, **P < 0.01, ***P < 0.001). Color indicates Spearman correlation coefficient (ρ), with red denoting positive and blue denoting negative correlations. (G) Kaplan–Meier analysis of progression-free interval (PFI) stratified by EZH2, Treg, and TAM (M2) status in TCGA-PRAD (cutoffs as defined in Methods; log-rank test). Tick marks indicate censored observations; numbers at risk are shown below the plot. The x-axis is truncated at 5 years for clarity.

Article Snippet: Cells were treated with the EZH2 inhibitor tazemetostat (MedChemExpress, HY-13803) dissolved in DMSO; vehicle controls received an equivalent volume of DMSO.

Techniques: Single Cell, Biomarker Discovery, Comparison, Expressing

Journal: Frontiers in Immunology

Article Title: Integrative bulk and single-cell transcriptomics link EZH2 to immunosuppressive programs and tumor–Treg crosstalk in castration-resistant prostate cancer

doi: 10.3389/fimmu.2026.1725097

Figure Lengend Snippet: EZH2-linked IMDEGs enable risk modeling and immune subtyping of PCa. (A) Analysis workflow. Tumors were stratified by EZH2 (top 30 vs bottom 30; left), followed by DEG identification (center) and correlation with Treg/TAM signatures (Spearman; |r| ≥ 0.4, nominal P < 0.05) to derive IMDEGs (right; schematic network). (B) GO Biological Process enrichment of IMDEGs. The x-axis shows −log10(nominal P). Dot size denotes gene count; color indicates BH-adjusted P values. (C) Non-zero model coefficients of the final gene signature. Coefficients were obtained from the selected survival model fitted in the training cohort, and the risk score was computed as a weighted linear sum of gene expression levels using these coefficients. (D) Kaplan–Meier analysis of PFI in the training cohort. Patients were stratified into high- and low-risk groups based on the median risk score. The P value from the log-rank test is shown. Tick marks indicate censored observations. (E) Consensus Non-negative Matrix Factorization (NMF) clustering of IMDEGs with k=6. The consensus matrix shows pairwise sample co-clustering frequencies (0–1). Sample annotations indicate assigned subtype and silhouette width (range shown). Rank-selection diagnostics are provided in . (F) Heatmap of prognosis-associated IMDEGs (row-scaled expression) across assigned subtypes. Rows represent individual IMDEGs and columns represent patients ordered by NMF-derived immune subtype. Expression values are row-wise z-scores, with red indicating higher-than-average and blue indicating lower-than-average expression within the cohort. (G) Heatmap of immune modulators across subtypes. The color scale represents row-wise z-scored expression, and column ordering is the same as in (F) . The left annotation indicates immune-modulator categories.

Article Snippet: Cells were treated with the EZH2 inhibitor tazemetostat (MedChemExpress, HY-13803) dissolved in DMSO; vehicle controls received an equivalent volume of DMSO.

Techniques: Gene Expression, Selection, Expressing, Derivative Assay

Journal: Frontiers in Immunology

Article Title: Integrative bulk and single-cell transcriptomics link EZH2 to immunosuppressive programs and tumor–Treg crosstalk in castration-resistant prostate cancer

doi: 10.3389/fimmu.2026.1725097

Figure Lengend Snippet: Single-cell transcriptomics identifies a malignant EZH2^high program marked by proliferation and suppression of interferon/immune-response pathways. (A) UMAP of scRNA-seq from CSPC and CRPC tumors with major lineages annotated. (B) Dot plot of EZH2 across lineages in CSPC and CRPC; color indicates average expression and dot size the percent of cells expressing, with significance denoted by asterisks (two-sided Wilcoxon rank-sum test; BH-adjusted P; ***q<0.001). (C, D) Malignant cell calling by copy-number inference: scatter of CNA correlation versus CNA signal separates malignant (red) from non-malignant (green) cells (C) ; corresponding heatmap of inferred CNAs across cells (D, E) Feature plots of EZH2 expression distribution across malignant and non-malignant cell clusters. (F) Volcano plot of DEGs between malignant EZH2^high and EZH2^low cells (two-sided Wilcoxon; min.pct = 0.1, logfc.threshold = 0.25, BH-adjusted P < 0.05). (G) Hallmark gene set enrichment analysis (GSEA) comparing malignant EZH2^high versus EZH2^low cells; bars show normalized enrichment scores (NES), with positive NES enriched in EZH2^high and negative NES enriched in EZH2^low.

Article Snippet: Cells were treated with the EZH2 inhibitor tazemetostat (MedChemExpress, HY-13803) dissolved in DMSO; vehicle controls received an equivalent volume of DMSO.

Techniques: Single-cell Transcriptomics, Expressing

Journal: Frontiers in Immunology

Article Title: Integrative bulk and single-cell transcriptomics link EZH2 to immunosuppressive programs and tumor–Treg crosstalk in castration-resistant prostate cancer

doi: 10.3389/fimmu.2026.1725097

Figure Lengend Snippet: Treg expansion and EZH2-linked malignant–Treg communication in CRPC. (A) UMAP of T cells from CSPC and CRPC ( GSE264573 ) with major subsets annotated. (B) Fractional composition of T-cell subsets. For each sample, the proportion of each T-cell subset was calculated as the number of cells assigned to that subset divided by the total number of T cells in the sample. Group differences in T-cell subtype proportions (CSPC vs CRPC) were tested using the propeller method (speckle), a limma empirical Bayes moderated t-test (two-sided) on transformed proportions, with BH FDR correction. Asterisks denote significance (* q < 0.05). (C) Dot plots of EZH2 and FOXP3 expression in Tregs from CSPC and CRPC samples. Dot size indicates percent expressed and color indicates average scaled expression. (D, E) GO Biological Process enrichment of genes positively (D) or negatively (E) correlated with EZH2 in Tregs. Correlations were assessed by metacell-based correlation analysis (see Methods; |r| ≥ 0.4, nominal P < 0.05) and GO enrichment significance is shown as BH-adjusted P (q values) in the color scale; dot size denotes gene count. (F) CellPhoneDB ligand–receptor analysis (mean>2; permutation P<0.05) for malignant–Treg pairs in CSPC and CRPC. Dot size and color indicate interaction mean expression level (as defined by CellPhoneDB). Significant interactions were identified by permutation testing (* P < 0.05, ** P < 0.01, *** P < 0.001). (G) Metacell-based correlation heatmaps linking EZH2 with malignant-cell ligands (left) and Treg receptors (right) (Pearson; ** nominal P < 0.01, *** nominal P < 0.001).

Article Snippet: Cells were treated with the EZH2 inhibitor tazemetostat (MedChemExpress, HY-13803) dissolved in DMSO; vehicle controls received an equivalent volume of DMSO.

Techniques: Transformation Assay, Expressing

Journal: Frontiers in Immunology

Article Title: Integrative bulk and single-cell transcriptomics link EZH2 to immunosuppressive programs and tumor–Treg crosstalk in castration-resistant prostate cancer

doi: 10.3389/fimmu.2026.1725097

Figure Lengend Snippet: EZH2 inhibitor perturbation analysis and cross-validation with malignant-cell programs. (A) Immunoblot of H3K27me3 and total H3 in C42 cells treated with EZH2 inhibitor (EZH2i) at the indicated concentrations, with densitometric quantification shown as the H3K27me3/H3 ratio (line plot). (B) Principal component analysis (PCA) of RNA-seq expression profiles (all expressed genes) comparing C42_Control and C42_EZH2i groups. (C) Volcano plot of differentially expressed genes (DEGs) between C42_EZH2i and C42_Control. Upregulated genes are shown in red, downregulated genes in blue, and non-significant genes in gray (two-sided Wald test in DESeq2; BH-adjusted P < 0.05 and |log2FC| ≥ 0.585). The top 5 upregulated (NEAT1, MALAT1, CYP1A1, SOX8, MUC3A) and top 5 downregulated (TXNRD2, ALDH1B1, PMPCA, PCCB, CPT2) genes are labeled (ranked by BH-adjusted P among significant DEGs). (D) Venn diagram showing overlap between malignant-cell DEGs from single-cell analysis (EZH2^high vs EZH2^low) and genes downregulated by EZH2i in C42 cells; representative overlapping genes are listed. (E) Venn diagram showing overlap between genes downregulated in EZH2^high malignant cells and genes upregulated by EZH2i in C42 cells; top3 enriched KEGG pathways for the overlapping set are shown on the right. (F) RNA-seq expression (TPM) of selected genes in Control versus EZH2i conditions. Box plots show median and IQR; points represent biological replicates. Differential expression was assessed using the two-sided Wald test in DESeq2 with BH-adjusted P values; significance is indicated as **q < 0.01 and ***q < 0.001. (G) RT–qPCR validation of selected genes in Control versus EZH2i conditions. Data are shown as mean ± SD (n = 3 biological replicates); between-group comparisons were performed using two-sided Student’s t-test; ***P < 0.001. GAPDH was used as the internal control and relative expression was calculated using the 2^-ΔΔCt method.

Article Snippet: Cells were treated with the EZH2 inhibitor tazemetostat (MedChemExpress, HY-13803) dissolved in DMSO; vehicle controls received an equivalent volume of DMSO.

Techniques: Biomarker Discovery, Western Blot, RNA Sequencing, Expressing, Control, Labeling, Single-cell Analysis, Quantitative Proteomics, Quantitative RT-PCR