MiR-381-3p inhibits Warburg effect and progression in osteosarcoma via targeting PFKFB3

Osteosarcoma (OS) is a primary bone malignancy; however, its exact mechanism of development remains largely unknown. Recent studies have shown that miR-381-3p can affect the development of various cancers. However, its biological effects and mechanisms of OS progression have not yet been elucidated. This study aimed to examine the biological role of miR-381-3p in OS. We screened differentially expressed microRNAs in OS using bioinformatics tools. miR-381-3p expression was assessed by quantitative real-time-polymerase chain reaction, and the effect of miR-381-3p on OS growth was evaluated in vitro and in vivo by functional assays. The direct interaction between PFKFB3 and miR-381-3p was validated by dual luciferase reporter assay. Finally, metabolic alterations in OS cells were monitored using an XF96 Metabolic Flux Analyzer. miR-381-3p expression was significantly downregulated in OS samples and cells. miR-381-3p also participated in suppressing OS cell growth and was associated with the Warburg effect. The PFKFB3 gene, encoding an essential glycolytic enzyme, was identified as a downstream gene of miR-381-3p, and PFKFB3 overexpression partly rescued the inhibitory impact of miR-381-3p on OS growth. miR-381-3p directly targets and negatively regulates PFKFB3 expression, thereby inhibiting OS proliferation by controlling the Warburg effect. The miR-381-3p/PFKFB3 axis may be a promising therapeutic target for OS.