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Fig. 6 VEGF-A-cGAS cascade induces angiogenesis by regulating miR-212-5p-ARPC3 regulatory loop (A and B) Heatmap (A) and the top 20 (B) differentially expressed miRNAs in Tg(fli1a:eGFP);cgas−/− and Tg(fli1a:eGFP) larvae. (C) qRT-PCR confirmation of top 20 enriched miRNAs (n = 3 replicates). (D) The relative miRNA levels of miR-212-5p and miR-15a-3p in cGAS KO and vector control HUVECs (n = 3 replicates). (E and F) The relative miRNA levels of miR-15a-3p (E) and miR-212-5p (F) in cGAS KO and vector control HUVECs with or without VEGF-A stimulation for 12 h (n = 3 replicates). (G) The relative miRNA levels of miR-212-5p control vector, GFP-FLAG-cGAS-ΔNLS, and GFP-FLAG-cGAS vectors transfected cGAS KO HUVECs (n = 3 replicates). (H) Schematic illustration of the predicted hsa-miR-212-5p binding site for targeting WT and mutant sequences of ARPC3 3′UTR. (I) Luciferase reporter assays in HEK293 cells co-transfected with luciferase reporter vectors containing WT or mutant sequences of ARPC3 3′UTR, and 50 nM miR-212-5p inhibitor or negative control (n = 3 replicates). (J and K) Tube formation (J) and quantification (K) in ARPC3 KO and vector control HUVECs with or without in-miR-212-5p and/or VEGF-A treatment and in ARPC3-overexpressing HUVECs with or without VEGF-A stimulation (n = 3 replicates). Scale bar, 200 μm. (L and M) Scratch migration (L) and quantification (M) in ARPC3 KO or vector control HUVECs with or without in-miR-212-5p treatment, as well as in ARPC3-overexpressing HUVECs at different time points (n = 3 replicates). Scale bar, 500 μm. Data are represented as means ± SEM. ANOVA in all analyses. ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001; ns, not significant. See also Figure S5 and Tables S6 and S7.