Fig. 1: IRhom1 is involved in chemoresistance.

a Correlation of iRhom1 gene expression levels with survivals in BRCA-TNBC or COAD patients receiving chemotherapy. For BRCA-TNBC-Chemo: n(Low expression) = 52, n (High expression) = 33; For COAD-Chemo: n (Low expression)=89, n(High expression) = 56. b CTRP-based prediction of the correlation between iRhom1 gene expression levels and the responses to different types of anticancer drugs. HDACi: histone deacetylase inhibitor, MAi: microtube assembly inhibitor, Topoi: topoisomerase inhibitor, PLK1i: polo-like kinase 1 inhibitor, NAMPTi: nicotinamide phosphoribosyltransferase inhibitor. c The impact of siRNA-mediated iRhom1 knockdown on the cytotoxicity of DOX or CPT-SAHA in several cancer cell lines. n = 6 independent samples. d Changes in protein levels of iRhom1 following treatment with DOX or CPT-SAHA. n = 4 independent experiments and data were quantified by densitometry. e RNA-seq analysis of gene enrichment in various signaling pathways in iRhom1 KO CT26 cells compared to WT cells. f Changes in the protein levels of MAPK14-HSP27 axis in iRhom1 KO cells compared to WT cells. n = 5 independent experiments and data were quantified by densitometry. g Changes in the protein levels of MAPK14-HSP27 axis in iRhom1 OE cells compared to WT cells. n = 5 independent experiments and data were quantified by densitometry. h Changes in the protein levels of MAPK14-HSP27 axis after treatment with various concentrations of CPT-SAHA in iRhom1 KO cells and WT cells. n = 3 independent experiments and data were quantified by densitometry. i MTT cytotoxicity assay of treatments with various concentrations of CPT-SAHA in CT26 WT or CT26 iRhom1 OE cells, with or without knockdown of MAPK14 respectively. n = 6 independent samples. j Synergy between Ivermectin (IVM) and chemotherapy drug (CPT-SAHA or DOX). k Immunoprecipitation of HA-iRhom1 with anti-HA beads led to pulldown of p-38α (MAPK14) in HA-iRhom1 expressing 293 T cells and reciprocal immunoprecipitation of FLAG-MAPK14 with anti-FLAG beads led to pulldown of iRhom1 in FLAG-MAPK14 expressing 293 T cells. Data are presented as mean ± s.e.m. in (c, i) and mean ± s.d. in (d, f, g). Statistical analysis was performed by log rank test for comparison in (a), two-tailed Student’s t-test for comparison in (c, f, g), and one-way ANOVA with Tukey’s post hoc test for comparison in (d and i). Data are representative of two independent experiments in (e), i–k three independent experiments in (c, h), four independent experiments in (d), and five independent experiments in (f, g). Source data are provided as a Source Data file for (c, d, f, g, h, i, j, k).