Background
Circular RNAs (circRNAs) are abnormally expressed in breast cancer (BC). However, the biological function and mechanism of circHMCU still need to be further explored.
Conclusion
CircHMCU acted as an oncogenic factor by regulating the miR-4458/PGK1 axis in BC.
Methods
The expression levels of circHMCU, miR-4458 and phosphoglycerate kinase 1 (PGK1) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The glucose uptake, lactate production and ATP level were assayed by related commercial kits. Cell Counting Kit-8 (CCK8), 5'-ethynyl-2'-deoxyuridine (EdU) and flow cytometry assays were used to test cell proliferation and apoptosis, respectively. The migratory and invasive abilities were detected by transwell and wound-healing assays. The relationships among circHMCU, miR-4458 and PGK1 were verified by dual-luciferase reporter assay. The function of circHMCU in tumor growth was evaluated by animal studies.
Results
CircHMCU was upregulated in BC tissues and cell lines, whereas miR-4458 was downregulated. For biological experiments, circHMCU knockdown inhibited cell proliferation, migration, glycolysis, while promoted cell apoptosis. CircHMCU bound miR-4458, and miR-4458 targeted PGK1. MiR-4458 inhibition reversed circHMCM knockdown-mediated effects on BC cell malignant behaviors. MiR-4458 overexpression suppressed cell glycolysis, proliferation, and metastasis and promoted apoptosis in BC cells through PGK1 upregulation. Additionally, circHMCU suppressed tumor growth in vivo.