Fig. 5: PROTAC-6272 induces cellular senescence independently of methylation. | Oncogene

Fig. 5: PROTAC-6272 induces cellular senescence independently of methylation.

From: EZH2 PROTACs outperform catalytic inhibitors in prostate cancer by targeting a methylation-independent function of PRC2

Fig. 5: PROTAC-6272 induces cellular senescence independently of methylation.The alternative text for this image may have been generated using AI.

A VCaP cells were subjected to triplicate RNA-seq analysis upon 48 h of treatment with DMSO, PROTAC-6286, PROTAC-6272, and EPZ-6438 (1 µM). Heatmap shows differentially expressed genes regulated by PROTAC-6272. Gene ontology (GO) analysis reveals the top 10 HALLMARK concepts induced and repressed by PROTAC-6272. B Gene Set Enrichment Analysis (GSEA) was performed to determine the enrichment of two public cellular senescence gene sets, SAUL_SEN_MAYO (n = 124) and FRIDMAN_SENESCENCE_UP (n = 77), in the gene expression dataset of VCaP cells treated with DMSO or PROTAC-6272. C SA-β-gal staining to test cell senescence in 22Rv1 and VCaP cells treated with 1 µM of PROTAC-6272 for 48 h. SA-β-Gal positive cells (red arrows) were displayed in light blue and quantified as a percentage of total cells in randomly selected fields (ns, not significant;, ∗∗∗p < 0.001, n = 6). D Flow cytometry analysis of cell cycle progression in 22Rv1 and VCaP cells. E 22Rv1 and VCaP cells were treated with DMSO, PROTAC-6272, and EPZ for 48 h. CDKN1A (p21) expression in each cell line was quantified from RNA-seq data using RPKM (***p < 0.001, n = 3). F 22Rv1 and VCaP cells were treated with DMSO, PROTAC-6272, and EPZ (1 µM) for 48 h. Protein lysates were collected and probed with the indicated antibodies in immunoblotting analysis.

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