Hsa_circ_0092276 promotes doxorubicin resistance in breast cancer cells by regulating autophagy via miR-348/ATG7 axis

• Published in: Translational oncology 2021-08, Vol.14 (8), p.101045-101045, Article 101045
• Main Authors: Wang, Qiuli, Liang, Dong, Shen, Peng, Yu, Yang, Yan, Yuan, You, Wei
• Format: Article
• Language: English
• Subjects: Autophagy; Breast cancer; Doxorubicin; Drug resistance; hsa_circ_0092276/miR-348/ATG7; Original Research
• ISSN: 1936-5233; 1936-5233
• DOI: 10.1016/j.tranon.2021.101045

•Hsa_circ_0092276 promotes ADM resistance in breast cancer cells.•Hsa_circ_0092276 enhances ADM resistance by promoting autophagy.•Hsa_circ_0092276 regulates ATG7 expression via sponging miR-384.•Hsa_circ_0092276 promotes autophagy and ADM resistance via miR-384/ATG7 axis.•Hsa_circ_0092276 enhances ADM resistance in breast cancer in vivo. Previous study has confirmed that hsa_circ_0092276 is highly expressed in doxorubicin (DOX)-resistant breast cancer cells, indicating that hsa_circ_0092276 may be involved in regulating the chemotherapy resistance of breast cancer. Here we attempted to investigate the biological role of hsa_circ_0092276 in breast cancer. We first constructed DOX-resistant breast cancer cells (MCF-7/DOX and MDA-MB-468/DOX). The 50% inhibiting concentration of MCF-7/DOX and MDA-MB-468/DOX cells was significantly higher than that of their parental breast cancer cells, MCF-7 and MDA-MB-46. MCF-7/DOX and MDA-MB-468/DOX cells also exhibited an up-regulation of drug resistance-related protein MDR1. Compared with MCF-7 and MDA-MB-46 cells, hsa_circ_0092276 was highly expressed in MCF-7/DOX and MDA-MB-468/DOX cells. Hsa_circ_0092276 overexpression enhanced proliferation and the expression of LC3-II/LC3-I and Beclin-1, and repressed apoptosis of breast cancer cells. The effect of hsa_circ_0092276 up-regulation on breast cancer cells was abolished by 3-methyladenine (autophagy inhibitor). Hsa_circ_0092276 modulated autophagy-related gene 7 (ATG7) expression via sponging miR-384. Hsa_circ_0092276 up-regulation promoted autophagy and proliferation, and repressed apoptosis of breast cancer cells, which was abolished by miR-384 overexpression or ATG7 knockdown. In addition, LV-circ_0092276 transfected MCF-7 cell transplantation promoted autophagy and tumor growth of breast cancer in mice. In conclusion, our data demonstrate that hsa_circ_0092276 promotes autophagy and DOX resistance in breast cancer by regulating miR-348/ATG7 axis. Thus, this article highlights a novel competing endogenous RNA circuitry involved in DOX resistance in breast cancer.