Fig. 7: Chemotherapy-induced dsRNA is sensed by ZBP1 in noncancerous tissues from the patients with CRC. | Cell Death & Disease

Fig. 7: Chemotherapy-induced dsRNA is sensed by ZBP1 in noncancerous tissues from the patients with CRC.

From: Sensing of endogenous retroviruses-derived RNA by ZBP1 triggers PANoptosis in DNA damage and contributes to toxic side effects of chemotherapy

Fig. 7

a Various types of human cancer cell lines were lysed and immunoblotted with anti-ZBP1 and anti-GAPDH antibodies. b Normal colonic and tumorous tissues from CRC patients were lysed and immunoblotted with indicated antibodies. c IHC analysis of dsRNA expression in normal colonic tissues from CRC patients with/out chemotherapy (n = 10 for each group). Scale bar, 200 μm. The complete set of images is presented in Supplementary Fig. 7. d Quantification of dsRNA expression level in the samples from (c). e Normal colonic tissues from (c) were examined by PLA assay with anti-ZBP1 antibody and anti-dsRNA J2 antibody, or f anti-RIPK3 antibody, or g anti-Casp-6 antibody. Representative images of the PLA assay were shown. Arrowheads indicate the PLA speck. h A working model of ZBP1-derived PANoptosis in DNA damage. ERVs are activated by DNA damage and sensed by ZBP1 to trigger RIPK3-Casp6-mediated PANoptosome assembly and PANoptosis. The activation of ZBP1-derived PANoptosis further contributes to chemotherapy-induced toxicity. Bar graphs represent the mean ± SD from three independent experiments. Statistical analysis was performed using a two-sided student’s t-test. NS, not significant; **p < 0.005 (two-way ANOVA).

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