Fig. 4: miR-181a promotes DNA damage and drives genomic instability.

a GSEA of significantly altered gene sets associated with genomic instability in pmiR-181a cells. Heatmap (left) of normalized enrichment scores for either pmiR-181a vs pscram-miR or pmiR-181a + antimiR vs pscram-miR. Bar graph of FDR q-values for the pmiR-181a and pmiR-181a + antimiR GSEA results. The red line indicates the significance cut-off of 0.25. Multiple testing adjustments were made using FDR correction according to default GSEA parameters. b Representative immunofluorescence micrographs of γH2AX staining in pscram-miR, pmiR-181a, and pmiR-181a + antimiR cells. Purple indicates staining of actin with ActinRed, red indicates staining of nuclei with DAPI, green indicates staining of γH2AX foci. c Plot showing inverse correlation between the number of γH2AX foci for a cell nucleus and the corresponding circularity of the same cell nucleus. Spearman correlation coefficients and p values are displayed. d Genomap of copy number variants detected by SNP array in pscram-miR, pmiR-181a, and pmiR-181a + antimiR cells with color key below. e Graph depicting percent of the genome altered in pscram-miR, pmiR-181a, and pmiR-181a + antimiR cells. Inset graph shows the % genome altered of the FT cell lines in the context of % genome altered distribution for TCGA HGSOC patients. N = 2 for all cell lines. f Graph showing the number of events for each CNV subtype in pscram-miR, pmiR-181a, and pmiR-181a + antimiR cells. Inset graph shows the total number of CNV events for pscram-miR, pmiR-181a, and pmiR-181a + antimiR cells. N = 2 for all cell lines. g Fraction of the genome amplified in pscram-miR, pmiR-181a, and pmiR-181a + antimiR cells. N = 2 for all cell lines. h Fraction of the genome with loss of heterozygosity in pscram-miR, pmiR-181a, and pmiR-181a + antimiR cells. N = 2 for all cell lines. All data are representative of N = 3 independent experiments unless otherwise stated. The measure of center for the error bars is given as the mean value. Two-sided Student’s t test was used unless otherwise stated. Error bars indicate ±standard deviation. *p < 0.05, **p < 0.005, ***p < 0.0005.