Hsa_circ_0000591 drives osteosarcoma glycolysis and progression by sequestering miR‐194‐5p and elevating HK2 expression

Abstract

AbstractOsteosarcoma (OS) is the most common bone tumour with a high risk of metastatic progression and recurrence after treatment. Circular RNA hsa_circ_0000591 (circ_0000591) plays a compelling role in OS aggressiveness. However, the function and regulatory mechanism of circ_0000591 need to be further elucidated. As a subject of this study, a differential circRNA circ_0000591 was screened by circRNA microarray expression profiling (GSE96964). Expression changes of circ_0000591 were detected using real‐time quantitative polymerase chain reaction (RT‐qPCR). Effects of circ_0000591 silencing on OS cell viability, proliferation, colony formation, apoptosis, invasion, and glycolysis were determined via functional experiments. The mechanism by which circ_0000591 functions as a molecular sponge for miRNAs was predicted using bioinformatics analysis and validated using dual‐luciferase reporter and RNA pull‐down assays. Xenograft assay was done to validate the function of circ_0000591. Circ_0000591 was strongly expressed in OS samples and cells. Silencing of circ_0000591 lessened cell viability, repressed cell proliferation, invasion, glycolysis, and promoted cell apoptosis. Importantly, circ_0000591 regulated HK2 expression by serving as a miR‐194‐5p molecular sponge. MiR‐194‐5p silencing impaired circ_0000591 downregulation‐mediated suppression of OS cell malignancy and glycolysis. HK2 overexpression weakened the inhibiting impacts of miR‐194‐5p on OS cell malignancy and glycolysis. Also, circ_0000591 silencing decreased xenograft tumour growth in vivo. Circ_0000591 drove OS glycolysis and growth by upregulating HK2 by sequestering miR‐194‐5p. The study highlighted the tumour‐promoting function of circ_0000591 in OS.