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. 2024 Jun 15;15(6):418. doi: 10.1038/s41419-024-06814-3

Fig. 2. Inhibiting LINC00152 overcomes tamoxifen resistance by inducing tamoxifen-dependent ferroptosis.

Fig. 2

A, B The nuclear vs. cytoplasmic localization of LINC00152 in MCF-7 (A) and T47D (B) Par and TamR cells. MALAT1 and DANCR were used as controls for nuclear and cytoplasmic RNAs, respectively. C Percent cell viability inhibition in MCF-7.TamR cells expressing shLINC00152 upon treatment with tamoxifen. D GSEA analysis showing the ferroptosis-related genes enriched in low LINC00152-expressing ER+ breast cancer patients treated with endocrine therapy from GSE87411. E Pearson correlation analysis of LINC00152 expression with ferroptosis score in ER+ patients from GSE58644. F, G The levels of ferroptosis score before and after endocrine therapy in sensitive (F) and resistant (G) ER+ patients from GSE87411. H Percentage cell viability inhibition in shLINC00152-expressing MCF-7.TamR cells treated with tamoxifen with or without 0.1 µM of liproxstatin-1 (Lipro). I Relative intracellular Fe2+ levels in shCtrl or shLINC00152-expressing MCF-7.TamR cells that were treated with 7.5 µM tamoxifen for 1.5 h. J Lipid peroxidation assay in T47D.TamR cells transfected with siLINC00152 (siLINC) in combination with tamoxifen, showing fold change of lipid peroxidation. Cumene was used as a positive control. K Western blot analysis of the negative regulators of ferroptosis, xCT, GPX4, and FTH1 in MCF-7.TamR cells expressing shLINC00152 and treated with tamoxifen. Actin is used as a loading control in all Western blots unless stated otherwise. L Percentage cell viability inhibition in shLINC00152-expressing MCF-7.TamR cells transfected with GPX4 or xCT open reading frame (ORF). M, N Percentage cell viability inhibition in MCF-7.TamR (M) and T47D.TamR (N) cells treated with tamoxifen alone or in combination with 3 or 5 µM RSL3. Data are presented as mean values ± standard deviation (SD). P-values for (D) were calculated using the GSEA software (Broad Institute) while others were calculated with the paired (cell viability) or unpaired (others), two-tailed Student’s t-test. *P < 0.05, **P < 0.01, n.s. not significant.