Hsa_circ_0097922 promotes tamoxifen resistance and cell malignant behaviour of breast cancer cells by regulating ACTN4 expression via miR-876-3p.

Abstract

An increasing number of findings have verified the critical roles of circular RNAs (circRNAs) in human cancers, and chemotherapy resistance is a poor prognostic factor for breast cancer (BC). This study is designed to explore the function of hsa_circ_0097922 in the tamoxifen resistance of breast cancer. Hsa_circ_0097922, microRNA-876-3p (miR-876-3p), and alpha-actinin 4 (ACTN4) level were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell survival, proliferation, apoptosis, migration and invasion were detected by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry, wound healing and Transwell assays. Protein levels of proliferating cell nuclear antigen (PCNA), B-cell lymphoma-2 (Bcl-2), cleaved caspase 3, matrix metalloproteinase 9 (MMP9), and ACTN4 were determined using western blot assay. Using bioinformatics software, the binding between miR-876-3p and hsa_circ_0097922 or ACTN4 was predicted, followed by confirmation by RNA immunoprecipitation (RIP) and RNA pull-down assays. A xenograft tumour model in vivo analysed the biological role of hsa_circ_0097922 on BC tumour growth and drug resistance. Hsa_circ_0097922 and ACTN4 were increased, and miR-876-3p was decreased in tamoxifen resistance BC cells. Moreover, hsa_circ_0097922 knockdown can block BC cell malignant behaviour and tamoxifen resistance in vitro. Mechanically, hsa_circ_0097922 acted as a sponge of miR-876-3p to regulate ACTN4 expression. Hsa_circ_0097922 silencing increased the drug sensitivity of BC in vivo. Hsa_circ_0097922 might regulate BC cell malignant behaviour and tamoxifen resistance partly by regulating the miR-876-3p/ACTN4 axis, hinting at a promising therapeutic target for the BC treatment.