Background
Breast 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.
Conclusion
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. Key points: Significant 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.
Methods
The 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.
Results
Circ_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.