Fig. 2. circATXN7 identification and its involvement in AICD.
A The schematic of screening target circRNA which was related to NF-κB/AICD axis. B Heatmap of differentially expressed circRNAs in lactic acid- versus PBS-treated Day-1 T cells (n = 3 independent samples). C Statistics of anti-CD3-induced specific apoptosis for Day-6 T cells transduced with lentivirus carrying an expression cassette for circATXN7 shRNA (sh1 or sh2) or shRNA control vector (shVec) (n = 3 independent experiments). Ut, Day-6 T cells without any treatment. D Statistics of anti-CD3-induced specific apoptosis for Day-6 T cells transduced with lentivirus carrying an expression cassette for sh1 or shVec, with or without lactic acid (10 mM) treatment (n = 3 independent experiments). E Western blots showing global histone lactylation and H3K18la levels in tumor-specific CTLs from KRASWT or KRASMUT CRCs (n = 3 samples). F Immunoprecipitated lactylated proteins determined by western blots for H3K18la. Three independent experiments were performed and similar results were obtained. G Representative IGV tracks showing enriched H3K18la modification at the ATXN7 promotor by ChIP-seq analysis of 10 mM lactic acid-treated Day-1 T cells. H ChIP-qPCR analysis for H3K18la status at the ATXN7 promotor of Day-1 T cells treated with 10 mM lactic acid, or lactic acid (10 mM) in combination with 10 nM AZD3965 (n = 3 independent experiments). Ut, Day-1 T cells without any treatment. I ChIP-qPCR analysis for EP300 status at the ATXN7 promotor of Day-1 T cells treated with 10 mM lactic acid, or lactic acid (10 mM) in combination with 10 nM AZD3965 (n = 3 independent experiments). Ut, Day-1 T cells without any treatment. J circATXN7 expression levels in Day-1 T cells treated with indicated concentrations of lactic acid (n = 3 independent experiments). Statistical data presented in this figure show mean values ± SD (C, D, H–J). **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001 and ns indicates p > 0.05, by one-way ANOVA (C, D, H–J). Source data and exact p values are provided as a Source Data file.