Silencing of circUSPL1 represses breast cancer progression by targeting miR‐1296‐5p/MTA1 axis

Abstract

Abstract Background The effect of circular RNAs (circRNAs) is widely studied in various human cancers, including breast cancer (BC). Herein, circUSPL1 has been recognized as a new regulator for BC progression. However, the detailed biological function and molecular mechanism of circUSPL1 in BC remain vague. Methods The expression level of circUSPL1, miR‐1296‐5p and metastasis associated 1 (MTA1) was examined by quantitative reverse transcription PCR. BC cell proliferation, migration, invasion, apoptosis and aerobic glycolysis were analyzed by colony formation assay, 5‐ethynyl‐2′‐deoxyuridine assay, wound healing assay, transwell assay, flow cytometry and glycolysis corresponding kits, respectively. The protein level of Bcl‐2, Bax, HK2, GLUT1 and MTA1 was evaluated by western blot analysis. The relationship of miR‐1296‐5p and circUSPL1 or MTA1 was affirmed using dual‐luciferase reporter or RIP assays. A murine xenograft model was conducted to analyze the tumor growth in vivo. Results CircUSPL1 and MTA1 expression level was increased, but miR‐1296‐5p was particularly reduced in BC tissues and cells. CircUSPL1 deficiency significantly inhibited BC cell proliferation, migration, invasion, glycolysis, and promoted cell apoptosis. In addition, circUSPL1 directly targeted miR‐1296‐5p, and downregulation of miR‐1296‐5p eliminated the inhibitory action of circUSPL1 knockdown. Additionally, overexpression of miR‐1296‐5p repressed cell malignant properties, while the suppressive effects were overturned by MTA1 elevation. Lastly, silencing of circUSPL1 inhibited tumor growth by sponging miR‐1296‐5p and regulating MTA1. Conclusion CircUSPL1 deficiency repressed BC cell malignant phenotypes through reducing MTA1 via targeting miR‐1296‐5p, which might provide a theoretical basis for BC treatment.

Keywords

• breast cancer
• circUSPL1
• miR‐1296‐5p
• MTA1