Circular RNA 0007255 regulates the progression of breast cancer through miR‐335‐5p/SIX2 axis

AbstractBackgroundBreast cancer (BC) is a common cancer in women worldwide. Emerging evidence has indicated that circular RNA hsa‐circ_0007255 (circ_0007255) is a prognostic mediator in BC progression. However, the functional role of circ_0007255 needs to be determined.MethodsThe expression of circ_0007255, microRNA (miR)‐335‐5p, and SIX Homeobox 2 (SIX2) was evaluated using quantitative real‐time polymerase chain reaction (qRT‐PCR) or western blot assay. Actinomycin D and RNase R treatment was performed to analyze the stability of circ_0007255. Additionally, Seahorse extracellular flux, colony formation and transwell analyses were carried out to detect oxygen consumption ratio (OCR), colony formation and cell mobility, respectively. The interaction between miR‐335‐5p and circ_0007255 or SIX2 was confirmed via dual‐luciferase reporter assay. A xenograft tumor model was established to explore the role of circ_0007255 in vivo.ResultsCirc_0007255 and SIX2 were overexpressed, but miR‐335‐5p was diminished in BC tissues and cells. Circ_0007255 absence inhibited oxygen consumption, colony formation, cell migration and invasion, and these effects were particularly abrogated via miR‐335‐5p upregulation in BC cells. Moreover, SIX2 deficiency eliminated the promotion effects of miR‐335‐5p inhibitor on oxygen consumption, colony formation, and cell mobility in BC cells. Importantly, circ_0007255 inhibited tumor growth in vivo. Mechanically, circ_0007255 was a sponge of miR‐335‐5p to regulate SIX2 expression in BC progression.ConclusionCirc_0007255 functioned as a novel oncogene in the progression of BC by regulating miR‐335‐5p/SIX2 axis, and might be a promising biomarker for BC treatment.Key pointsSignificant findings of the study: Levels of circ_0007255 and SIX2 were upregulated, but miR‐335‐5p was diminished in BC tissues and cells. Circ_0007255 was an oncogene in BC development and exerted its function via miR‐335‐5p/SIX2 axis in BC. Tumor growth was reduced by circ_0007255 absence.What this study adds: Circ_0007255 functioned as a novel oncogene in the progression of BC by regulating miR‐335‐5p/SIX2 axis, and might be a promising biomarker for BC treatment.