Circ-RPPH1 knockdown retards breast cancer progression via miR-328-3p-mediated suppression of HMGA2

Abstract

BackgroundCircular RNA Ribonuclease P RNA Component H1 (circ-RPPH1) was confirmed to act as an oncogene in many cancers to promote cancer progression. However, the exact function and mechanism of circ-RPPH1 in breast cancer (BC) remain vague. MethodsThe expression of circ-RPPH1, microRNA (miR)-328-3p and high-mobility group AT-hook 2 (HMGA2) was detected using quantitative real-time polymerase chain reaction and western blot. Cell viability, apoptosis, migration and invasion were determined using cell counting kit-8 assay, flow cytometry and transwell assay, respectively. Glucose metabolism was calculated by detecting glucose uptake and lactate production. The target correlations between miR-328-3p and circ-RPPH1 or HMGA2 were confirmed by dual-luciferase reporter assay. The murine xenograft model was established to conduct in vivo experiments. ResultsCirc-RPPH1 expression was elevated and miR-328-3p was decreased in BC tissues and cells. Circ-RPPH1 knockdown or miR-328-3p re-expression suppressed cell proliferation, migration, invasion and glycolysis but induced apoptosis in BC in vitro. Circ-RPPH1 was a sponge of miR-328-3p, and silencing of miR-328-3p reversed the inhibitory effects of circ-RPPH1 knockdown on BC cell malignant phenotypes and glycolysis. MiR-328-3p directly targeted HMGA2, and HMGA2 overexpression abolished the action of miR-328-3p in BC cells. Besides, circ-RPPH1 could regulate HMGA2 expression by miR-328-3p in BC cells. Moreover, murine xenograft model analysis suggested circ-RPPH1 knockdown inhibited tumor growth in vivo. ConclusionCirc-RPPH1 knockdown retarded cell malignant phenotypes and glycolysis via miR-328-3p/HMGA2 axis in BC, providing a potential therapeutic target for BC treatment.