A Novel circ_0104345/miR-876-3p/ZBTB20 Axis Regulates the Proliferation, Migration, Invasion, and Apoptosis of Breast Cancer Cells.

Abstract

Breast cancer (BC) is one of the most common malignant tumors in women. CircRNA/miRNA/mRNA regulatory axes have been shown to be involved in the pathogenesis of BC. Here, we sought to analyze the functional mechanism of circ_0104345 in BC. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the levels of circ_0104345, miR-876-3p and zinc finger and BTB domain containing 20 (ZBTB20) mRNA. Cell Counting Kit-8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to test cell viability and proliferation, respectively. Cell migration was tested by wound healing assay, and cell invasion was examined by transwell assay. Tube formation ability was tested by angiogenesis assay. Flow cytometry was applied for cell apoptosis. Western blot assay was utilized to measure the protein expression. The relationship between miR-876-3p and circ_0104345 or ZBTB20 was identified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Xenografts in mice were conducted to analyze the effect of sh-circ_0104345 on tumor growth in vivo. Circ_0104345 and ZBTB20 were upregulated and miR-876-3p expression was decreased in BC. Circ_0104345 knockdown inhibited cell proliferation, migration, invasion, and enhanced cell apoptosis. MiR-876-3p was targeted by circ_0104345. MiR-876-3p depletion reversed the effects of circ_0104345 downregulation on the progression of BC cells. ZBTB20 was regulated by circ_0104345 through miR-876-3p. The effects of miR-876-3p on BC cell behaviors were restored by ZBTB20 increase. The results of in vivo experiments indicated that silencing of circ_0104345 blocked the growth of xenograft tumors. In this study, we demonstrated, for the first time, the crucial regulation of the new circ_0104345/miR-876-3p/ZBTB20 axis in the biological phenotypes of BC cells.