Journal: Cell Reports Medicine

Article Title: HIF-activated priming of TRAIL-induced cell death determines epigenetic vulnerability in kidney cancer

doi: 10.1016/j.xcrm.2026.102630

Figure Lengend Snippet: dDNMT activates TRAIL-death receptor signaling in VHL -deficient ccRCC cells (A) Volcano plot of SGI1027-induced and -repressed genes in RCC10 cells ( n = 2 biological replicates). FC, fold change. (B) Biocarta pathway enrichment analysis of SGI1027-induced genes in RCC10 cells. (C) RT-qPCR analysis of TNFSF10 , TNFRSF10A , TNFRSF10B , and TNFRSF10D mRNA levels in RCC10 cells treated with vehicle or SGI1027 for 2 days ( n = 3 biological replicates). (D and E) Immunoblot analysis of TRAIL, DR4, DR5, DcR2, pro-caspase-10, and cleaved caspase-10 (C-caspase-10) proteins in isogenic RCC10 cells treated with vehicle, SGI1027 (D and E, n = 2 biological replicates), MS1129 (E, n = 2 biological replicates), or decitabine (E, n = 2 biological replicates) for 2 or 7 days. (F) Global m5C levels in RCC10 cells treated with vehicle or SGI1027 for 2 days by ELISA assay ( n = 3 biological replicates). (G–J) MeDIP-qPCR assay in RCC10 cells treated with vehicle or SGI1027 for 2 days ( n = 3 biological replicates). (K–M) DNMT1, DNMT3A, and DNMT3B ChIP-qPCR assay in RCC10 cells ( n = 3 biological replicates). (N) Scheme of dDNMT-activated apoptotic pathway. Data represent mean ± SEM. p value was determined by bioinformatics with edgeR (A) or gene set enrichment analysis (B), unpaired 2-tailed Student’s t test (C and F), two-way ANOVA with Tukey’s test (G–I), and one-way ANOVA with Dunnett’s test (K–M). See also and .

Article Snippet: anti-DR4 antibody , Proteintech , 24063-1-AP, RRID: AB_2879421.

Techniques: Quantitative RT-PCR, Western Blot, Enzyme-linked Immunosorbent Assay, Methylated DNA Immunoprecipitation, ChIP-qPCR

Journal: Cell Reports Medicine

Article Title: HIF-activated priming of TRAIL-induced cell death determines epigenetic vulnerability in kidney cancer

doi: 10.1016/j.xcrm.2026.102630

Figure Lengend Snippet: dDNMT specifically kills patient-derived VHL -deficient ccRCC in mice (A) Tumor growth curves of VHL -deficient UTSW-PDX206, UTSW-PDX258, UTSW-PDX490, and UTSW-PDX26 in mice treated with vehicle (Veh) or SGI1027 for 10 days. (B) Tumor growth curves of VHL -WT UTSW-PDX416 and UTSW-PDX143 in mice treated with vehicle or SGI1027 for 10 days. (C) Kaplan-Meier survival curve of UTSW-PDX490-bearing mice ( n = 10 biological replicates). (D and E) Global m5C levels in UTSW-PDX206 (D) or UTSW-PDX258 (E) tumors harvested from mice after treatments by ELISA assay ( n = 5 biological replicates). (F) Immunoblot analysis of DNMT1, DNMT3A, DNMT3B, TRAIL, DR4, DR5, procaspase-10, C-caspase-3, and C-caspase-7 proteins in UTSW-PDX258 tumors harvested from mice after treatments ( n = 5 biological replicates). (G) Representative C-caspase-3 IHC in UTSW-PDX258 tumors. Scale bar, 100 μm. (H) Quantification of C-caspase-3-positive cells in (G) ( n = 5 biological replicates). (I) Immunoblot analysis of DNMT1, DNMT3A, DNMT3B, TRAIL, DR4, DR5, C-caspase-3, and VHL proteins in UTSW-PDX416 tumors harvested from mice after treatments ( n = 5 biological replicates). (J) Immunoblot analysis of DNMT1, DNMT3A, DNMT3B, and procaspase-10 proteins in UTSW-PDX206, UTSW-PDX258, and UTSW-PDX26 tumors ( n = 4–5 biological replicates). Data represent mean ± SEM. p value was determined by two-way ANOVA with Tukey’s test (A), log rank test (C), and unpaired 2-tailed Student’s t test (D, E, and H). See also and ; .

Article Snippet: anti-DR4 antibody , Proteintech , 24063-1-AP, RRID: AB_2879421.

Techniques: Derivative Assay, Enzyme-linked Immunosorbent Assay, Western Blot