Fig. 1: High expression of wild-type IDH2 in TNBC is essential to support tumor growth.

a–c Analysis of IDH2 expression in a breast cancer tissues (n = 388) and normal tissues (n = 61, Oncomine breast cancer datasets dataset), b across different subtypes of breast cancer tissues (normal n = 333, LumA n = 511, LumB n = 416, basal n = 315, Survexpress breast cancer datasets), or c different disease stages (Stage I n = 92, stage II n = 299, stage III n = 112, Survexpress breast cancer datasets). d Censored Cox analysis of Kaplan–Meier survival curves of TNBC patients (n = 316) stratified by IDH2 high- and low-expression groups, which were analyzed for relapse-free survival using the median value of IDH2 expression as the cut-off (Kmplot). e–h Colony number (e), cell number (f), cell viability (g), and apoptosis ratio (h) of MDA-MB-231 cell stably transfected with IDH2 shRNA (#1 and #2) or non-targeting control shRNA (NC). The samples for western blot analysis of IDH2 and β-actin were derived from the same experiment and analyzed in parallel in separate gels. Colonies were counted on day 14 (n = 3 for each condition, technical replicates, representative of two independent experiments (original data included in the Source Data). i Apoptosis in HCC38 cells transfected with IDH2 shRNA or control shRNA. Cell death was quantified using Annexin V-FITC/PI staining followed by flow cytometry analysis, n = 3 for each condition (technical replicates, representative of two independent experiments, original data included in the Source Data). j Western blot analysis of key survival proteins (BCL2 and MCL-1) in MDA-MB-231 or HCC38 cells transfected with IDH2 shRNA (#1 and #2) or non-targeting control shRNA (NC). The samples derived from the same experiment but different gels (one gel for BCL2, another for MCL-1, and another for β-actin) were processed in parallel. Images are representative of two independent experiments (original data included in Source Data)；k Tumor incident and tumor size of Balb/C-nude mice implanted with MDA-MB-231 cells without or with IDH2 knockdown. The difference between the NC control group and the IDH2 knockdown groups (sh#1 or sh#2) was analyzed using the Chi-square test (SPSS version 17, n = 14 for each group, independent biological repeats). l Tumor growth curves of xenografts in Balb/C-nude mice implanted with MDA-MB-231 cells stably transfected with IDH2 shRNA (#1) or control shRNA (NC), n = 7 for each group, independent biological repeats; two-way ANOVA test was employed for statistical analysis, ****p ≤ 0.0001. Error bars in all panels represent mean ± SD. A two-sided Student’s t-test was employed for statistical analysis. *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001.