Abstract
This study aims to explore the mechanism of Circular RNA CDR1as implicating in regulating 5-fluorouracil (5-FU) chemosensitivity in breast cancer (BC) by competitively inhibiting miR-7 to regulate CCNE1. Expressions of CDR1as and miR-7 in 5-FU-resistant BC cells were determined by RT-PCR. CCK-8, colony formation assay and flow cytometry were applied to measure half maximal inhibitory concentration (IC50), 5-Fu chemosensitivity and cell apoptosis. Western blot was used to detect the expressions of apoptosis-related factors. CDR1as was elevated while miR-7 was inhibited in 5-FU-resistant BC cells. Cells transfected with si-CDR1as or miR-7 mimic had decreased IC50 and colony formation rate, increased expressions of Bax/Bcl2 and cleaved-Caspase-3/Caspase-3, indicating inhibition of CDR1as and overexpression of miR-7 enhances the chemosensitity of 5-FU-resistant BC cells. Targetscan software indicates a binding site of CDR1as and miR-7 and that CCNE1 is a target gene of miR-7. miR-7 can gather CDR1as in BC cells and can inhibit CCNE1. In comparison to si-CDR1as group, CCNE1 was increased and chemosensitivity to 5-Fu was suppressed in si-CDR1as + miR-7 inhibitor group. When compared with miR-7 mimic group, CDR1as + miR-7 mimic group had increased CCNE1 and decreased chemosensitivity to 5-Fu. Nude mouse model of BC demonstrated that the growth of xenotransplanted tumour in si-CDR1as + miR-7 inhibitor group was faster than that in si-CDR1as group. The tumour growth in CDR1as + miR-7 mimic group was faster than that in miR-7 mimic group. CDR1as may regulate chemosensitivity of 5-FU-resistant BC cells by inhibiting miR-7 to regulate CCNE1.