Circular RNA ATP2C1 (has_circ_0005797) sponges miR-432/miR-335 to promote breast cancer progression through regulating CCND1 expression

Breast cancer (BC) is the most frequently diagnosed malignancy in the world. Accumulating evidence has indicated that circular RNAs (circRNAs) play essential roles in BC. Here we investigated the biological functions of circATP2C as a competing endogenous RNA (ceRNA) in BC development. We found that circATP2C1 expression was upregulated in BC cells and tissues and was significantly associated with the poor overall survival in BC patients. CircATP2C1 is more resistant to RNase R exonuclease and Actinomycin D than is the linear mRNA of ATP2C1. CircATP2C1-knockdown inhibited the viability, colony proliferation and invasion abilities, while increasing the apoptosis rates of BC cells in vitro, as well as inhibiting tumor mass, size and weight in vivo. Upregulation of miR-432 and miR-335 inhibited CCND1 expression in BC cells. Both miR-432/miR-335 specifically bind to the 3'-UTR of circATP2C1 and CCND1 (CyclinD1). The inhibition of the aggression of BC cells by circATP2C1-knockdown was rescued by co-transfection of miR-432/miR-335 inhibitors. In conclusion, circATP2C1 promotes BC oncogenesis and metastasis by sponging miR-432/miR-335 to abolish the inhibition of the target gene, CCND1. This study suggests that circATP2C1 has implications for BC diagnosis and treatment.