Fig. 2: Association of RPS24 ex4:3 bp isoforms with ER signaling. | Experimental & Molecular Medicine

Fig. 2: Association of RPS24 ex4:3 bp isoforms with ER signaling.

From: RPS24 microexon isoform as a novel biomarker for estrogen receptor-positive breast cancer progression and therapeutic resistance

Fig. 2

a Comparison of RPS24 AS isoform expression between breast cancer cell line molecular subtypes. Cell lines are categorized into four types on the basis of ER and HER2 expression. The y-axis represents the proportion of each isoform. P values derived from analysis of variance tests are shown for each plot. b Association of the ex4:3 bp isoform with the ESR1 gene. Columns sort cell lines by ex4:3 bp expression (green). Lower rows show ESR1 mRNA expression and two gene dependency scores (KO by RNAi or CRISPR) in the corresponding cell lines. Correlation with ex4:3 bp is displayed on the right. c Changes in ex4:3 bp expression due to ESR1 gene mutations. GSE108304: T47D cell line with Y537S and D538G mutations, treated with ethanol or 10 nM estrogen (estradiol, E2) for 4 h or 24 h. GSE112243: MCF7 with E380Q, Y537S and D538G mutations, with or without 24 h of estrogen (E2) treatment. Differences between ESR1 wild type and mutants were analyzed using a t-test (***P < 0.0005, **P < 0.005, *P < 0.05). d ER-alpha interactions with RPS24 at multiple levels (GSE173631, MCF7 cells). Left: proteins interacting with ESR1 in the cytoplasm, identified by immunoprecipitation followed by mass spectrometry. The x-axis shows median log2 fold change (ER-alpha/immunoglobulin G (IgG)) in protein abundance between ER-alpha immunoprecipitation and IgG control, with higher values indicating stronger interactions with ER-alpha. The y-axis shows −log10(Best.Expect.Val), with higher values indicating greater statistical confidence of protein identification. Right: a heat map showing that RPS24 (highlighted at bottom) is among ESR1-bound mRNAs essential for breast cancer cell fitness, as determined by CRISPR interference of ESR1-binding sites. The top 15 genes were selected on the basis of Mann–Whitney P value, and each cell value represents the average phenotype of the three strongest single-guide RNAs on cell growth across day 5, 9 and 14 time points compared with day 0. Negative values indicate stronger growth inhibition.

Back to article page