Fig. 2 | Nature Communications

Fig. 2

From: Discovery and preclinical evaluation of anti-miR-17 oligonucleotide RGLS4326 for the treatment of polycystic kidney disease

Fig. 2

RGLS4326 inhibits miR-17 and de-represses direct miR-17 targets. a RGLS4326 (green triangle) dose-responsively inhibits miR-17 in HeLa cell luciferase assay 24 h after transfection, with an EC50 value of 28.3 ± 4.0 nM (mean ± standard deviation, n = 7 independent experiments). b RGLS4326 dose-responsively de-represses multiple miR-17 target genes (as measured by miR-17 PD-Sig) in mouse IMCD3 cells 24 h after transfection, with an EC50 value of 77.2 ± 20.2 nM (n = 4 independent experiments). cd RGLS4326 treatment results in de-repression of the direct miR-17 target genes, Pkd1 and Pkd2 in IMCD3 cells (n = 3). e RGLS4326, but not control oligo, functionally inhibited miR-17 and de-repressed miR-17 PD-Sig in six cell lines derived from normal (DBA-WT, M1, MDCT, LTL-WT) or PKD (DBA-PKD and LTL-PKD) mouse kidneys after 24 h treatment by transfection at 30 nM (n = 3) and in f normal mouse kidney tissue slice culture after 72 h ex vivo incubation at 10 μM (n = 4). Control oligo (grey triangle) containing the same chemical-modification, length, and design as RGLS4326, but different base pair sequence, was used as a negative control. Error bars represent standard deviations. *p < 0.05, ****p < 0.0001. One-way ANOVA, Dunnette’s multiple comparison test. Source data for Fig. 2af is provided in Source data files

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