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. 2021 Jan 4;131(1):e139929. doi: 10.1172/JCI139929

Figure 4. Enhanced de novo GTP synthesis promotes Pol I activity in chemoresistant SCLC cells.

Figure 4

(A) Gene sets associated with IMPDH2 mRNA across human cancers in the TCGA database. All KEGG gene sets were included in the analysis. (B) Median OP-Puro signal in DMS53 treatment-naive and chemoresistant cells treated with vehicle or 1 μM MPA, with or without 20 μM guanosine for 12 hours. ***P < 0.001. (C) ATP, GTP, CTP, and UTP levels in DMS53-CR treated with vehicle or 5 μM MPA, with or without 10 μM guanosine for 8 hours. **P < 0.01, ****P < 0.0001. (D) Ribosome abundance in DMS53-CR treated with vehicle, 1 μM MPA, with or without 20 μM guanosine for 48 hours. (E) Abundance of Pol I, II, or III transcripts in DMS53-CR cells treated with vehicle or 5 μM MPA with or without 20 μM guanosine for 8 hours. ***P < 0.001. (F) Abundance of pre-rRNA and median OP-Puro signal in H82 treated with vehicle or 1 μM MPA, with or without 10 μM guanosine. ****P < 0.0001. (G and H) Abundance of GTP and pre-rRNA in DMS53-CR treated with vehicle or 5 μM MPA, with or without 1–5 μM cycloheximide for 6 hours. **P < 0.01, ****P < 0.0001. Data are shown as mean and SD (B, C, and F–H), mean and SEM (E). Statistical significance was assessed using 1-way ANOVA with Tukey’s multiple-comparison test (B, C, and E–H). All experiments were repeated twice or more.