Circular RNA circMET contributes to tamoxifen resistance of breast cancer cells by targeting miR-204/AHR signaling

Breast cancer is a prevalent female malignancy and tamoxifen remains the first-line treatment for breast cancer, but tamoxifen resistance is a frequent clinical problem. Circular RNAs (circRNAs) are a bunch of noncoding RNAs with circular structures and play crucial roles in cancer development. Here, we aimed to explore the unreported function of circMET in the modulation of tamoxifen resistance of breast cancer cells. The expression of circMET was upregulated in tamoxifen-resistant breast cancer cells. The deple-tion of circMET significantly reduced the cell viability and proliferation in tamoxifen-resistant breast cancer cells and the co-treatment of tamoxifen promoted the effect. Mechanically, the luciferase activity of circMET and was repressed by miR-204-5p and AHR 30UTR in the cells. The expression of miR-204-5p was elevated by circMET knockdown. The expression of AHR was downregulated by miR-204-5p or circMET depletion, while the miR-204-5p inhibitor reversed the effect of circMET depletion in cells. The overexpression of circMET enhanced the cell viability and proliferation of MCF7-Re and T47D-Re cells but miR-204-5p or AHR depletion blocked the phenotype. Clinically, the expression of circMET and AHR has enhanced in tamoxifen-resistant samples compared with tamoxifen sensitive samples, but miR-204-5p presented a revered expression in the samples. Consequently, we concluded that circular RNA circMET contributed to tamoxifen resistance of breast cancer cells by targeting miR-204-5p/AHR signaling. (C) 2022 Published by Elsevier Inc.

Automated summary

This study investigated the role of circular RNA circMET in modulating tamoxifen resistance in breast cancer cells, and found that circMET promotes tamoxifen resistance by targeting the miR-204-5p/AHR signaling pathway.