Research Paper Volume 12, Issue 20 pp 20658—20683

Cross-talk between the ER pathway and the lncRNA MAFG-AS1/miR-339-5p/ CDK2 axis promotes progression of ER+ breast cancer and confers tamoxifen resistance

Figure 6. lncRNA MAFG-AS1 and CDK2 promote tamoxifen resistance. (A, B) Kaplan-Meier plotter survival analysis of RFS (HR = 3.09, p = 0.04) and DMFS (HR = 6, p = 0.0027) with the patients treated with adjuvant tamoxifen monotherapy (exclude all chemotherapy). Samples were stratified into “high” and “low” MAFG- AS1 expression based on median cutoff value in each dataset. (C) qRT-PCR analysis of the expression of MAFG-AS1 and ESR1 in parental MCF-7 and TamR MCF-7. (D) qRT-PCR analysis of the expression of MAFG-AS1 in T47D and MCF-7 cells with the duration of tamoxifen. (E) Proliferation assay in parental MCF-7 cells and in TamR MCF-7 cells following siRNA-mediated knockdown of MAFG-AS1 via two independent siRNAs. (F) Kaplan-Meier plotter survival analysis of DMFS (HR = 1.97, p=0.00067) with the patients treated with adjuvant tamoxifen monotherapy by different CDK2 expression. (G) Proliferation assay in parental MCF7 cells and in TamR-MCF7 cells following siRNA-mediated knockdown of CDK2 via two independent siRNAs. (H) MTT assay performed for T47D cells overexpressing vector control and MAFG-AS1 with 1uM tamoxifen. (IK) Tumor volume and weight confirmed the truth of MAFG-AS1 promotes tamoxifen resistance in vivo experiment. (L) Possible molecular mechanisms of the MAFG-AS1/ miR-339-5p/CDK2 axis and positive feedback loop in luminal breast cancer.