Fig. 1: AI-resistant ER-positive breast cancer exhibits enhanced aerobic glycolysis with lncRNA DIO3OS upregulation.

a Heatmap of expression profile sequencing for breast cancer tissues obtained from patients that were either sensitive or resistant to AI treatment. n = 7 biological replicates. b GSEA results of the differential gene expression profiles between AI-resistant and AI-sensitive breast cancer. c, d Glucose uptake (c) and lactate production (d) of MCF-7/T47D LTED cells in comparison with their parental counterparts. e, f ECAR values and calculated glycolytic capacity of MCF-7 LTED (e) and T47D LTED (f) cells compared with their parental counterparts. g LC-MS analysis of MCF-7 LTED cells in comparison with parental MCF-7 cells. h Volcano plot of lncRNA sequencing data for breast cancer tissues from patients that were either sensitive or resistant to AI treatment. i qRT-PCR of the top ten lncRNA candidates in two AI-resistant cell models. j qRT-PCR of lncRNA DIO3OS in breast tumor tissues from patients that were sensitive or resistant to AI treatment. Means ± s.d. of n = 13 biological replicates are shown. k Representative ISH images of DIO3OS in paraffin-embedded breast cancer tissues and the correlation analysis (mean ± s.e.m.) between DIO3OS level and AI treatment response. Tumor tissues were obtained from ER-positive breast cancer patients that were either sensitive (n = 133) or resistant (n = 124) to AI treatment. Scale bars, 50 μm. l Statistical analysis of AI-resistant and AI-sensitive breast tumor tissues under different DIO3OS expression status in cohort. m Kaplan–Meier survival curve for relapse-free survival and overall survival in AI-treated ER-positive breast cancer patients with high (n = 112) or low (n = 145) DIO3OS expression in tumor tissues. HR hazard ratio. n Heatmap of the association of the different clinical characters (tumor size, Ki67 index, and metastatic status) with DIO3OS high-expressing and DIO3OS low-expressing AI-treated breast tumors. Means ± s.d. of n = 3 (c, d, g, i) or n = 4 (e, f) independent experiments yielding similar results are presented, and P-values were determined by two-tailed Student’s t-test (c–g, i, j), Mann–Whitney test (k), χ2 test (l, n), or log-rank test (m). Source data are provided as a Source Data file.