CircRNA circYY1 (hsa_circ_0101187) Modulates Cell Glycolysis and Malignancy Through Regulating YY1 Expression by Sponging miR-769-3p in Breast Cancer.

Abstract

BackgroundBreast cancer (BC) is a highly heterogeneous malignant tumor that affects women’s health. Circular RNAs (circRNAs) are involved in tumor growth in many cancers. However, the role of hsa_circ_0101187 (circYY1) in BC is still unclear.MethodsExpression of circYY1, microRNA (miR)-769-3p, and YY1 (Yin Yang 1) mRNA was tested by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability, colony formation, migration, and invasion were analyzed with MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), colony formation, and transwell assays. Glucose uptake, lactate product, and ATP (adenosine triphosphate) content were detected with corresponding kits. Several protein levels were measured with Western blotting. The regulatory mechanisms of the circYY1, miR-769-3p, and YY1 were validated by RNA immunoprecipitation (RIP) assay, dual-luciferase reporter assay, and/or RNA pull-down assay. The role of circYY1 in BC was confirmed by xenograft assay.ResultsCircYY1 and YY1 were upregulated in BC, while miR-769-3p had an opposing result. Also, BC patients with high circYY1 expression had a poor prognosis. Downregulation of circYY1 decreased xenograft tumor growth in vivo. Both circYY1 inhibition and miR-769-3p elevation constrained BC cell viability, colony formation, migration, invasion, and glycolysis in vitro. CircYY1 acted as a sponge for miR-769-3p, which targeted YY1. CircYY1 sponged miR-769-3p to modulate YY1 expression. Both miR-769-3p inhibition and YY1 upregulation antagonized circYY1 silencing-mediated influence on malignancy and glycolysis of BC cells.ConclusionCircYY1 promoted glycolysis and tumor growth via increasing YY1 expression through sponging miR-769-3p in BC, offering a promising therapeutic target and prognostic biomarker for BC.