Ge Gao1, Xiaoyan Li2, Jiabeini Zhang3, Hong Yu3. 1. Department of Pathology, China-Japan Union Hospital of Jilin University, Jilin University Changchun 130021, Jilin Province, China. 2. Department of Infection Management, Stomatological Hospital, Jilin University Changchun 130021, Jilin Province, China. 3. Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Jilin University Changchun 130021, Jilin Province, China.
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 IC50-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<0.05). CONCLUSION: Circ_0001946 absorbs miR-671-5p to target EGFR to promote the growth and malignant invasion of drug-resistant BC cells, thereby increasing the resistance to tamoxifen. This effect of circ_0001946 may be achieved by transcriptional activation of YY1. AJTR
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 IC50-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<0.05). CONCLUSION: Circ_0001946 absorbs miR-671-5p to target EGFR to promote the growth and malignant invasion of drug-resistant BC cells, thereby increasing the resistance to tamoxifen. This effect of circ_0001946 may be achieved by transcriptional activation of YY1. AJTR