Fig. 5: APA-linked susceptibility genes in breast cancer. | Nature Communications

Fig. 5: APA-linked susceptibility genes in breast cancer.

From: A distinct class of pan-cancer susceptibility genes revealed by an alternative polyadenylation transcriptome-wide association study

Fig. 5: APA-linked susceptibility genes in breast cancer.

a LocusZoom plot of breast cancer GWAS SNPs, eQTLs, sQTLs, and 3′aQTLs at the CRLS1 locus. SNPs are colored by LD (r2). b Region association plots for CRLS1. Breast cancer GWAS signal at the gene locus (gray) and the GWAS signal after removing the effects of target gene 3′UTR usage (black); results indicate that the association is largely explained by target gene 3′UTR usage. c Example of RNA-seq coverage plot for the CRLS1 3′UTR. d Box plot showing the distribution of the normalized PDUI values for each genotype, each dot in the box plot represents the PDUI value for one individual from the breast mammary tissue of GTEx project (n = 396). e Changes of 3′UTR usage in MCF-7 cells detected by 3′ RACE. The 3′ RACE strategy is shown in the upper panel. F and R indicate forward and reverse primers, respectively. The bar plot on the right shows the measured usage of dPAS. (n = 3; P = 0.0076). f Luciferase activity from a reporter system containing the short and long 3′UTR of CRLS1 in MCF-7 cells (n = 3; P = 0.0057). g Luciferase activity from a reporter system containing reference and alternative variant of 3′aQTL located within 3′UTR region in MCF-7 cells (n = 3; P = 0.023). h Proliferation of MCF-7 cells treated with the indicated siRNAs (n = 3; P = 0.0028). i Colony formation assay for MCF-7 cells treated with the indicated siRNAs. Left panel: Colonies were formed in 12-well plates and imaged on day 8 after siRNA treatment. Images are representative results from three independent experiments. Right panel: Quantification of colony numbers from the left panel (n = 3; P = 0.016). j Cell proliferation of shRNA-mediated knockdown cells was analyzed on days 1, 3, 5, and 7 (n = 3). k Schematic depicts alternative alleles of 3′UTR variants mediated 3′UTR lengthening promotes cancer progression. For panels e–j, the data shown are the mean ± s.d. from three independent experiments. P values were calculated using the two-tailed, paired Student’s t-test. Source data are provided as a Source Data file.

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