Figure 3 from Targeting TREX1 Induces Innate Immune Response in Drug-Resistant Small-Cell Lung Cancer

Immunogenicity is induced in TREX1 depleted cells through cGAS-STING activation. A, ELISA of human cGAMP level in cell lysates of Scr or sgTREX1 H69AR and H196 cells, treated with 0.5 µmol/L reversine or DMSO for 72 hours. B, ELISA of human IFNβ level in conditioned medium derived from Scr or sgTREX1 H69AR and H196 cells, treated with 5-µmol/L cisplatin or DMSO for 72 hours. C, Schematic of cGAS-STING pathway leading to IFN response. STING is a crucial mediator of the dsDNA sensing pathway. D, Expression levels of TREX1, STING, and p-IRF3 in H69AR and H196 cells were compared by immunoblotting between cells transfected with siCtrl and siTREX1 (#1) in Scr or sgSTING background. E, Expression levels of IFNB and IFIT1 genes were compared between cells transduced with Scr or STING sgRNA, after transfection with siCtrl and siTREX1 (#1; mean ± SEM; n = 3). F, Growth curves of H69AR and H196 cells [Scr or sgSTING, transfected with siCtrl or siTREX1 (#1)] were compared (mean ± SEM; n = 3). Data represent mean ± SEM. ns, not significant; *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001 by two-way ANOVA followed by Tukey’s multiple comparisons test (A, B, E, and F).