YX0798 disrupts cell cycling in MCL cells toward cell cycle arrest. (A) The bubble plots show top cancer hallmarks and signaling pathways downregulated (blue) or upregulated (red) upon CDK9 inhibition. (B) The FISCHER_G2_M_CELL_CYCLE pathway was significantly downregulated by YX0798 (50 and 100 nM) in JeKo-1 cells (6 and 24 hours) and Mino cells (6 hours). AZD4573 (10 nM) serves as a control. (C) YX0798 and AZD4573 induced cell cycle arrest in MCL cells as indicated. (D) Volcano plot shows the significantly altered genes associated with cell cycle arrest upon YX0798 treatment at 100 nM for 6 hours. (E) Representative genes AURKA and CCNA2 were significantly downregulated with CDK9is YX0798 or AZD4573. (F) Illustration of Aurora kinase A– and B–mediated cell cycle progression. (G) Western blots confirmed cell cycle disruption induced by treatment with YX0798 and AZD4573 for 6 hours. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. FC, fold change; FDR, false discovery rate; absNES, absolute normalized enrichment score; ns, not significant; P-H2AX, phosphorylated histone 2A variant; P-H3, phosphorylated histone 3.
Figure 5.

YX0798 disrupts cell cycling in MCL cells toward cell cycle arrest. (A) The bubble plots show top cancer hallmarks and signaling pathways downregulated (blue) or upregulated (red) upon CDK9 inhibition. (B) The FISCHER_G2_M_CELL_CYCLE pathway was significantly downregulated by YX0798 (50 and 100 nM) in JeKo-1 cells (6 and 24 hours) and Mino cells (6 hours). AZD4573 (10 nM) serves as a control. (C) YX0798 and AZD4573 induced cell cycle arrest in MCL cells as indicated. (D) Volcano plot shows the significantly altered genes associated with cell cycle arrest upon YX0798 treatment at 100 nM for 6 hours. (E) Representative genes AURKA and CCNA2 were significantly downregulated with CDK9is YX0798 or AZD4573. (F) Illustration of Aurora kinase A– and B–mediated cell cycle progression. (G) Western blots confirmed cell cycle disruption induced by treatment with YX0798 and AZD4573 for 6 hours. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. FC, fold change; FDR, false discovery rate; absNES, absolute normalized enrichment score; ns, not significant; P-H2AX, phosphorylated histone 2A variant; P-H3, phosphorylated histone 3.

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