Circular RNA AGFG1 motivates breast cancer cell proliferation, invasion, migration, and glycolysis by controlling microRNA-653-5p/14-3-3 protein epsilon

Abstract

A recent Pairwise meta-analysis confirmed that circular RNA AGFG1 (circAGFG1) is abnormally highly expressed in breast cancer (BC) and may be associated with death risk. The purpose of this study was to elucidate the biological role of circAGFG1 in BC and to explore its potential downstream molecular mechanisms. CircAGFG1, miR-653-5p and YWHAE expression in BC tissues and cells were analyzed by RT-qPCR or western blot. Gene expression was regulated by transfection of plasmids or oligonucleotides and the biological behaviors of BC cells were analyzed by a series of assays. The ring structure of circAGFG1 was analyzed by RNase R and actinomycin D treatment. Dual luciferase reporter assay and RNA-pull down were used to verify the targeting relationship of circAGFG1 and downstream factors. A nude mouse xenograft experiment was performed to verify the effect of circAGFG1 on cancer cells in vivo. The results showed that circAGFG1 and YWHAE were highly expressed in BC while miR-653-5p was lowly expressed. Both circAGFG1 and YWHAE had a targeting relationship with miR-653-5p. Knockdown of circAGFG1 inhibited BC cell proliferation, invasion, migration, and glycolysis. The inhibitory effect of circAGFG1 knockdown on BC was reversed by silencing miR-653-5p. The inhibitory effect of overexpression of miR-653-5p on malignant behaviors of BC cells was reversed by overexpression of YWHAE. Knockdown of circAGFG1 inhibited tumor growth in vivo. Taken together, these data suggest that circAGFG1 acts as a sponge for miR-653-5p to mediate YWHAE expression to promote the malignant behaviors of BC.