Abstract

Objective: To investigate the mechanism of circ_0001946 activated by transcription factor Yin Yang 1 (YY1), targeting miR-671-5p to regulate epidermal growth factor receptor (EGFR) and thereby participating in the chemotherapy resistance of breast cancer (BC) cells. Methods: Circ_0001946, which is differentially expressed in BC, was screened using gene expression omnibus. Dual luciferase assay and RNA immunoprecipitation were conducted to verify the relationship among circ_0001946/miR-671-5p/EGFR. A ChIP test confirmed that YY1 can be used as a transcription factor of circ_0001946 to specifically bind to its promoter. The expression of circ_0001946/miR-671-5p/EGFR regulatory axis in BC tissues and cell lines were evaluated using qRT-PCR. As for in vitro experiments, tamoxifen was used to establish a drug-resistant BC cell model. The effects of the regulatory axis on the proliferation, invasion and apoptosis of BC cells were studied using CCK-8, Transwell invasion assay and Annexin V-FITC/PI staining, so as to evaluate its effect on the sensitivity of BC cells to tamoxifen. Results: Circ_0001946 showed an abnormally high expression in BC tissues and tamoxifen resistant cells and was up-regulated in an IC 50 -dependent manner (both P<0.05). Circ_0001946 was activated by YY1 in drug-resistant BC cells. Knockdown of circ_0001946 significantly inhibited the proliferation, invasion and promoted apoptosis of drug-resistant BC cells (all P<0.05). Overexpression of circ_0001946 promoted the proliferation and invasion of drug-resistant BC cells and hindered their apoptosis, which could be partially reversed by miR-671-5p mimics (all P<0.05). EGFR has been proven to be a downstream target gene of miR-671-5p. A knockdown of EGFR improved the malignant biological behavior of drug-resistant BC cells, which could be partially eliminated by overexpression of circ_0001946 (all P<0.0