Fig. 4: JUN-RIBOTAC impairs pancreatic tumour cell proliferation and migration by selectively degrading JUN mRNA.
From: Programming inactive RNA-binding small molecules into bioactive degraders
a, Schematic of JUN degradation by targeting the JUN IRES. b, The structures of compounds used to target JUN mRNA. c, The effect of JUN-RIBOTAC and JUN-binder on JUN mRNA levels in MIA PaCa-2 cells after treatment for 72 h, as determined using RT–qPCR (n = 6 biological replicates). d, The effect of JUN-RIBOTAC on JUN protein levels in MIA PaCa-2 cells (n = 4 biological replicates). e, The effect of JUN-RIBOTAC on JUN mRNA levels in MIA PaCa-2 cells in which RNase L was knocked down by CRISPR (n = 3 biological replicates) and in the corresponding MIA PaCa-2 control cell line in which CRISPR editing was performed using a scrambled guide RNA (n = 4 biological replicates), as determined using RT–qPCR. f, The effect of JUN-RIBOTAC on the proliferation of MIA PaCa-2 cells (n = 6 biological replicates). g, The effect of JUN-RIBOTAC on the invasiveness of MIA PaCa-2 cells, as determined using a Boyden chamber assay (n = 2 biological replicates; 2 fields of view were quantified per replicate). Data are mean ± s.d. (c–f). Statistical significance was determined using two-tailed Student’s t-tests (d–f) and one-way analysis of variance (ANOVA) adjusted for multiple comparisons (c).
