TREX1 expression is induced in drug-resistant SCLC cell lines. A, Schematic of establishment of subpopulations from H69 SCLC cell line. B, Volcano plots of H3K27Ac ChIP-seq and ATAC-seq analyses comparing H69AR and H69 cells are shown. C, Venn diagrams for top-hits genes of H3K27Ac ChIP-seq and ATAC-seq, and genes listed in “GOBP_NEGATIVE_REGULATION_OF_IMMUNE_SYSTEM_PROCESS.” TREX1 was selected as one of the eight overlapped genes. D, ATAC-seq and H3K27Ac ChIP-seq analysis to compare H69, H69M, and H69AR cells. Results of the TREX1 gene region are shown. E, Expression levels of the TREX1 gene in H69, H69M, and H69AR cells were compared by qPCR (mean ± SEM; n = 3). F, Expression levels of TREX1, cGAS, and STING in H69, H69M, and H69AR cells were compared by immunoblotting. G, Expression levels of TREX1 in H69, DMS114 cells treated with etoposide (20 or 50 µmol/L) or DMSO were compared by immunoblotting. H, Drug sensitivity/resistance data of SCLC cell lines are summarized. Cells are lined up based on TREX1 expression levels. Data represent mean ± SEM. ns, not significant; *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001 by one-way ANOVA followed by Dunnett’s multiple comparisons test (E).
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Murayama et al. (2024) studied this question.
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