Fig. 6: Depletion of NAT10 induces dsRNA-mediated RIG-I-dependent signaling through the Myc/CDK2/DNMT1 pathway. | Nature Communications

Fig. 6: Depletion of NAT10 induces dsRNA-mediated RIG-I-dependent signaling through the Myc/CDK2/DNMT1 pathway.

From: Inhibition of tumor-intrinsic NAT10 enhances antitumor immunity by triggering type I interferon response via MYC/CDK2/DNMT1 pathway

Fig. 6

A The FPKM of individual genes of the CDK family from RNAseq data originating from WT and sgNAT10 TC1 tumor cells. Heatmap depicting the CDKs and illustrating gene expression (color-coded by log2FC) (n = 3 biologically independent samples); **P = 0.0065. B The FPKM of individual genes of the DNMT family from RNAseq data originating from WT and sgNAT10 TC1 tumor cells. Heatmap depicting DNMTs and illustrating gene expression (color-coded by log2FC) (n = 3 biologically independent samples); ***P = 0.0004. C Western blotting of DNMT1, CDK2, and NAT10 in matched WT, sgNAT10 TC1 (upper panel), and MCA205 (lower panel) tumor cells. β-actin was used as a loading control. D Representative immunofluorescence staining of dsRNA in WT, sgNAT10, sgCDK2, sgNAT10 Myc-rescued, and sgNAT10 Cdk2-rescued TC1 tumor cells was detected using confocal microscopy. Antibody J2 targeted dsRNA (labeled in red). The corresponding statistical diagrams are shown on the right. Statistical analysis was conducted using one-way ANOVA (n = 15 biologically independent samples); ***P < 0.001; **P = 0.0055. E Representative immunofluorescence staining of dsRNA in WT, sgNAT10, sgCDK2, sgNAT10 Myc-rescued, and sgNAT10 Cdk2-rescued MCA205 tumor cells was detected using confocal microscopy. The corresponding statistical diagrams are shown on the right. Statistical analysis was conducted using one-way ANOVA (n = 15 biologically independent samples); ***P < 0.001; **P = 0.0057. F Protein expression levels of NAT10 and RIG-I in vector, sgNAT10, and sgNAT10/RIG-I TC1 tumor cells determined by Western blotting (upper panel). mRNA expression levels of Ifnb1, Stat1, Tlr3, Ddx58, Ccl5, Ccl7, Tap1, and Mx2 by RT-PCR in vector, sgNAT10, and sgNAT10/RIG-I TC1 tumor cells (n = 3 biologically independent samples). From left to right, all *** indicate P < 0.001; *P = 0.0451. Unless specified otherwise, the data are presented as means ± SEM (error bar) and compared using the two-sided Student’s t test. Source data are provided as a Source Data file.

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