Fig. 3

RGLS4326 suppresses the growth of primary human ADPKD cysts in vitro. a Primary cyst cultures derived from human ADPKD donors were transfected with RGLS4326 at 100 nM for 24 h and harvested for RNA-seq analysis. Kolmogorov-Smironov test statistics comparing the cumulative distribution of global mRNA changes between RGLS4326-treated (inverted green triangle) vs. mock-treated (brown circle) samples indicated significant de-repression of predicted miR-17 target genes (as defined by TargetScanHuman v7.1) after RGLS4326 treatment. b For each subsequent experiment, functional inhibition of miR-17 was assessed by measuring de-repression of human miR-17 PD-Sig²⁷ in representative cyst samples (n = 1/treatment/dose) after 24 h transfection with RGLS4326 (shades of green) or control oligo (shades of grey) and prior to further culturing in 3D Matrigel for an additional 8 days. c Western blot analysis demonstrating increased expression of polycystin-1 (PC1) and polycystin-2 (PC2) 72 h following RGLS4326 treatment (n = 3). d–e Quantification and (f) representative images of 3D cyst formation showing a reduction in cyst count and proliferation 9 days following initial RGLS4326 treatment (n = 3). g–h Inhibition of miR-17 as measured by miR-17 PD-Sig correlates with anti-cyst and anti-proliferation activity (n = 4 independent experiments among 2 donors). R², p-values and 95% confidence interval limits (dotted lines) from corresponding linear regression models were shown. Error bars represent standard deviations. *p < 0.05, **p < 0.01, ****p < 0.0001. One-way ANOVA, Dunnette’s multiple comparison test. Source data for Fig. 3b–e, and g–h is provided in Source data files