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. 2023 May 17;14:2806. doi: 10.1038/s41467-023-38443-3

Fig. 6. PRMT1 inhibition increase PD-L1 in a cGAS-dependent manner.

Fig. 6

a Genetic ablation of Prmt1 elevates mPD-L1 expression. The stable CT26-tet-on-shPrmt1 cells were treated with DOX for 3 days to induce deletion of endogenous Prmt1, followed by immunoblot analysis. b PRMT1 inhibition elevates mPD-L1 expression. CT26 cells were treated with the indicated doses of MS023 or GSK3368715 for 48 hours, followed by immunoblot analysis. c Depletion of endogenous cGAS reduces mPD-L1 expression. d Genetic ablation of Prmt1 elevates mPD-L1 expression in a cGAS-dependent manner. CT26-tet-on-shPrmt1 cells as in a were infected with sgcGAS lentivirus and treated with DOX, followed by immunoblot analysis. e PRMT1 inhibition elevates mPD-L1 expression in a cGAS-dependent manner. The stable cell lines as in c were treated with MS023, followed by immunoblot analysis. f, g Immunoblot analysis of mPD-L1 (f) and quantification (g) in different organs/tissues of mice after i.p. administration of 50 mg/kg MS023 or vehicle for 14 days. h, i Immunoblot analysis of mPD-L1 (h) and quantification (i) in different organs/tissues of mice after gavage of 80 mg/kg GSK3368715 or vehicle for 14 days. j Correlation analysis of cGAS and PD-L1 protein expression in human BRCA cell lines. The protein levels were retrieved from DepMap. ER+: estrogen receptor positive; HER2+: human epidermal growth factor receptor 2 positive; ER+, HER2+: ER and HER2 double positive; ER−, HER2−: ER and HER2 negative. k, l Immunoblot analysis of PD-L1 and cGAS in a panel of BRCA (k) and TNBC cell lines (l). m Immunoblot analysis of MDA-MB-231 cells after stimulation with indicated doses of HT-DNA for 12 hours. n Genetic ablation of PRMT1 increases cGAS/STING DNA sensing signaling in MBA-MD-231 cells. MDA-MB-231 cells were infected with tet-on-shPRMT1 lentivirus and selected with 1 μg/mL of puromycin for 7 days. The stable cell lines were treated with DOX for 3 days, and stimulated with HT-DNA for 12 hours, followed by harvesting for immunoblot analysis. Data are presented as mean values ± SD, and two-tailed unpaired Student t test were used in for 6 g and i, n = 5.