Extended Data Fig. 8: 3’UTR splicing of CTNNB1 promotes COAD tumorigenesis.
From: Pan-cancer pervasive upregulation of 3′ UTR splicing drives tumourigenesis
a, Proportion of 3’UTR splicing events in all (left), and 41 matched tumor-normal samples (right) from the TCGA-COAD dataset. P-values: Mann-Whitney U test; n: number of RNA-seq samples analyzed. b,c, Kaplan-Meier survival analysis of TCGA-COAD samples based on the segmentation numbers of 3USPs (b) and total splicing events (c) (top and bottom half of samples ranked by numbers). n: number of patients analyzed. d, Proportion of CTNNB1 3’UTR splicing events in all normal and tumor samples from the TCGA-COAD dataset. n: number of RNA-seq samples analyzed. e, Comparison of the CTNNB1 3’SP transcript expression between paired normal and COAD clinical samples (n = 12 patient samples). f-i, Effect of ASO-mediated blocking of the 3’UTR splice site on CTNNB1 transcript expression by qPCR (n = 3 independent experiments) (f), and PCR (g), protein expression (h) and anchorage-independent growth (n = 3 independent experiments) (i) in DLD-1. j-m, Effect of siRNA-mediated knockdown of CTNNB1 on CTNNB1 transcript (n = 3 independent experiments) (j), CTNNB1 and WNT target proteins (k) and WNT target transcript (n = 3 independent experiments) (l) expression, and anchorage-independent growth (n = 3 independent experiments) (m) in DLD-1. ASO-NC: non-targeting control ASO; ASO-SS: splice site ASO; CDS: coding sequence; 3’FL: full length 3’UTR; 3’SP spliced 3’UTR. e,f,i,j,l,m, Mean ± SEM; unpaired Student’s t-test *p < 0.05, **p < 0.01, ***p < 0.001. g,h,k, Data shown represent three independent experiments.
