Fig. 7: Loss of SFPQ mediates activation of pathways of innate immunity.

A Enriched terms in SFPQ knock-down U-2 OS cells. UP, upregulated; DW, downregulated; ABS, absolute value terms. Circle size, number of genes; color code, −log₁₀ alterations (p-adjusted); enrichment p-values were computed using a one-sided Fisher’s exact and Benjamini-Hochberg FDR correction. B Network representation for 5 enriched biological terms in siSFPQ U-2 OS cells. Orange nodes, term names; black dots, individual genes. c Western blot of siRNA-transfected U-2 OS cells. D Quantitative RT-PCR of indicated genes in siSFPQ U-2 OS cells. E cGAS immunofluorescence analysis. Left panel, representative images. Right panel, percentage of micronuclei with cGAS staining. F Immunofluorescence on siRNA-transfected U-2 OS cells. Left panel, representative images. Right panel, quantification of pan-nuclear pIRF3 staining. G Quantification of micronuclei in U-2 OS cells stably expressing my-tagged, full-length or mutant SFPQ. Endogenous SFPQ was depleted using 5’UTR-specific siRNAs. H Micronuclei in U-2 OS cells after transfection with indicated siRNAs and expression of mCherry-tagged RNaseH1 or control-mCherry. I Quantitative RT-PCR analysis in siRNA-transfected U-2 OS cells expressing mCherry-tagged RNaseH1 or control-mCherry. Survival plot showing correlation between low SFPQ Z-score and improved patient overall survival (j) high signature score (Fig. 7b) and improved patient overall survival (K). L Correlation of expression between SFPQ and pro-inflammatory gene signature. Score based on mean Z-score trimmed at 20%. The p-value was obtained by Anova-test. Center, median (50th percentile); box bounds, Q1 (25th percentile), Q3 (75th percentile); whiskers, minimum and maximum non-outlier values; dots, individual samples. M Kaplan-Meier plot analysis based on innate immunity signature expression and survival. Yellow, low SFPQ expression (Status=0) and high signature expression (Signature=1); gray, high SFPQ expression (Status=1) and low signature expression (Signature=0). Patient numbers are shown. P-value was calculated using a two-sided log-rank (Mantel–Cox) test. D–I Data presented as mean values ± standard deviation. N, number of independent experiments; n, analyzed nuclei; statistical test, unpaired, two-sided Student’s t test; scale bar (5 μm) applies to all images; DAPI, 4’,6-diamidino-2-phenylindole. J–M patient data were obtained from the TCGA pan-cancer sarcoma dataset. Source data are provided with this paper.