Hsa_circ_0069094 knockdown inhibits cell proliferation, migration, invasion and glycolysis, while induces cell apoptosis by miR-661/HMGA1 axis in breast cancer.

Circular RNAs (circRNAs) are revealed to regulate breast cancer progression. This study aimed to investigate hsa_circ_0069094-mediated effects on breast cancer cell malignancy. Quantitative real time PCR was employed to evaluate the expressions of hsa_circ_0069094, miR-661 and high mobility group A1 (HMGA1). Western blot was performed to determine the protein expression of HMGA1 and proliferating cell nuclear antigen. Breast cancer malignant progressions were explained by cell counting kit-8 proliferation, cell colony formation, flow cytometry analysis, wound-healing and transwell assays. Cell glycolysis was assessed by detecting glucose take, lactate production and hexokinase 2 (HK2) protein level. The target relationship between miR-661 and hsa_circ_0069094 or HMGA1 was predicted by circular RNA interactome and targetscan online databases, and identified by dual-luciferase reporter and RNA immunoprecipitation assay. The effects of hsa_circ_0069094 knockdown on breast cancer growth in vivo were elucidated by in vivo tumor formation assay. Hsa_circ_0069094 and HMGA1 expression were significantly upregulated, while miR-661 expression level was downregulated in breast cancer tissues and cells relative to adjacent normal breast tissues or MCF-10A cells. Functionally, hsa_circ_0069094 knockdown inhibited cell glycolysis, proliferation, migration and invasion, whereas induced cell apoptosis in breast cancer, which was decreased by miR-661 inhibitor. Mechanistically, hsa_circ_0069094 regulated HMGA1 by sponging miR-661. Furthermore, hsa_circ_0069094 knockdown repressed tumor formation in vivo. Collectively, hsa_circ_0069094 knockdown repressed breast cancer cell carcinogenesis and cell glycolysis by regulating HMGA1 through sponging miR-661, which provided a new insight for studying the mechanism of hsa_circ_0069094 in modulating breast cancer development.