MicroRNA-382-5p inhibits osteosarcoma development and progression by negatively regulating VEZF1 expression.

Human osteosarcoma is the most frequent malignant primary bone tumor that mainly occurs in young adults and children. MicroRNAs (miRNAs/miRs) are abnormally expressed in human osteosarcoma and contribute to osteosarcoma initiation and development. The present study aimed to investigate the role of miR-382-5p in the nosogenesis of osteosarcoma and to identify a novel target for osteosarcoma treatment. miR-382-5p expression was detected in human osteosarcoma clinical tissues and cell lines, including 143B, U2OS and MG63, via reverse transcription-quantitative PCR analysis. Multiple bioinformatic prediction toowe used to identify the potential target genes of miR-382-5p and vascular endothelial zinc finger 1 (VEZF1), which were validated via the dual-luciferase reporter assay. MG63 and U2OS cells were transfected with miR-382-5p mimics. The Cell Counting Kit-8 assay was performed to assess cell proliferation, while the Transwell assay was performed to assess migration and invasion. Cell colony formation was measured via crystal violet staining, and apoptosis was assessed via Annexin V/propidium iodide staining. The wound healing assay was performed to assess the migratory ability of U2OS and MG63 cells. Antitumor effects of miR-382-5p were evaluated in nude mice xenografts using U2OS cells. The results demonstrated that miR-382-5p expression was markedly downregulated in human osteosarcoma tissues and cell lines compared with adjacent normal tissues. Transfection of miR-382-5p mimics into MG63 and U2OS cells significantly inhibited the malignant behaviors of cells, including decreased proliferation, migration, diminished colony formation and invasion, and promoted osteosarcoma cell apoptosis. Bioinformatics prediction indicated that VEZF1 is a direct target gene of miR-382-5p. Overexpression of VEZF1 restored osteosarcoma tumor development inhibited by miR-382-5p in vivo. In addition, overexpression of miR-382-5p restrained the growth of xenograft osteosarcoma in nude mice following co-transfection, and overexpression of VEZF1 attenuated the inhibitory effect of miR-382-5p in nude mice. miR-382-5p acted as a tumor suppressor gene and inhibited the malignant biological behaviors of human osteosarcoma cells and functions associated with directly targeting VEZF1. Taken together, these results suggest that the miR-382-5p/VEZF1 interaction has an important role in osteosarcoma development and progression, and thus may be used as a diagnostic and therapeutic target for osteosarcoma.