Molecular mechanism of miR-27a-3p targeting FBXW7 regulating the malignant behavior of osteosarcoma cells.
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BACKGROUND: Osteosarcoma is a malignant bone tumor with high incidence in children and adolescents, and its prognosis is generally poor. Current comprehensive treatments are limited by tumor recurrence, lung metastasis, and chemoresistance, necessitating further elucidation of the underlying molecular mechanisms and the development of novel therapeutic targets. MicroRNAs (miRNAs) participate in the malignant biological behavior of tumors by post-transcriptionally regulating target genes. Previous studies have shown that miR-27a-3p is highly expressed in osteosarcoma, but its specific function and regulatory mechanism in osteosarcoma remain unclear. This study aims to investigate the effects of miR-27a-3p on the biological behavior of osteosarcoma cells and explore its mechanism of action. METHODS: The expression levels of miRNA and protein were detected by real-time polymerase chain reaction (RT-PCR) and Western blot. Bioinformatics methods were used to predict whether there were binding sites between miR-27a-3p and FBXW7 genes, and the interaction between miR-27a-3p and target gene FBXW7 was verified by dual luciferase reporter assay. miR-27a-3p mimics and inhibitors were used to overexpress and knock down the expression of miR-27a-3p, and the overexpressed plasmid of FBXW7 and siRNA-FBXW7 were used to overexpress and knock down the expression of FBXW7. Cell proliferation, migration and apoptosis were detected by Cell Counting Kit-8 (CCK-8) assay, Transwell migration assay and flow cytometry. RESULTS: miR-27a-3p was highly expressed in osteosarcoma cells, and overexpression of miR-27a-3p promoted the proliferation and migration of osteosarcoma cells, and inhibited cell apoptosis. miR-27a-3p knockdown inhibited the proliferation and migration of osteosarcoma cells and promoted cell apoptosis. miR-27a-3p can target the expression of FBXW7 and affect the proliferation, migration and apoptosis of osteosarcoma cells. Low expression of FBXW7 in osteosarcoma cells, overexpression of FBXW7 inhibited the proliferation and migration of osteosarcoma cells, and inhibition of the expression of FBXW7 promoted the proliferation and migration of osteosarcoma cells. The mechanism may be related to the Wnt/β-catenin signaling pathway. CONCLUSIONS: The high expression of miR-27a-3p in osteosarcoma cells can negatively regulate FBXW7 to promote the proliferation and migration of osteosarcoma cells and inhibit cell apoptosis, suggesting a functional association between miR-27a-3p/FBXW7 axis and osteosarcoma cell malignant behavior.