miR-652 Inhibits the Proliferation, Migration, and Invasion of Osteosarcoma Cells by Targeting HOXA9 and Regulating the PI3K/Akt Signaling Pathway

OBJECTIVE: The aim of this study was to investigate the abnormal expression of miR-652 in osteosarcoma and its related mechanism. MATERIALS AND METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of miR-652 and HOXA9 in osteosarcoma tissues and normal tissues. A bioinformatics method was used to predict target genes of miR-652, and then luciferase reporter genes and western blot tests were used to verify expression of target genes. The miR-652 overexpression models were established by transfecting miR-652 mimics into osteosarcoma U-2OS cells, and HOXA9 overexpression models were simultaneously established by transfecting pcDNA3.1-HOXA9 into osteosarcoma U-2OS cells. Cell proliferation ability was detected by the CCK-8 assay, cell migration ability was detected by the scratch test, and cell invasion ability was detected by the Transwell invasion assay. Western blot tests were used to verify the expression of HOXA9, p-PI3K, p-AKT, MMP2 and MMP9. RESULTS: miR-652 and HOXA9 showed low expression and overexpression, respectively, in osteosarcoma tissues. Proliferation, invasion, and migration abilities of osteosarcoma cells and the level of protein expression of p-PI3K, p-Akt, MMP2, and MMP9 were significantly decreased with enhanced miR-652 expression (P < 0.01), while overexpression of HOXA9 reversed this situation. The results of dual-luciferase reporter gene showed that expression and activity of HOXA9 were downregulated accordingly, and the level of HOXA9 protein was decreased with enhancing miR-652 expression (P < 0.01). CONCLUSION: miR-652 may negatively regulate HOXA9 expression and inhibit the proliferation, migration, and invasion abilities of osteosarcoma cells through the PI3K/Akt signaling pathway.