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Elevated expression of microRNA-328-3p suppresses aggressive malignant behaviors via targeting matrix metalloprotease 16 in osteosarcoma
BACKGROUND: A previous study indicated that microRNA(miR)-328-3p upregulation might be critical for resveratrol-mediated suppression of metastatic ability in human osteosarcoma, implying its potential role in this malignancy. However, the clinical significance and the biological functions of miR-328...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430066/ https://www.ncbi.nlm.nih.gov/pubmed/30936722 http://dx.doi.org/10.2147/OTT.S195022 |
Sumario: | BACKGROUND: A previous study indicated that microRNA(miR)-328-3p upregulation might be critical for resveratrol-mediated suppression of metastatic ability in human osteosarcoma, implying its potential role in this malignancy. However, the clinical significance and the biological functions of miR-328-3p in osteosarcoma remain unclear. METHODS: miR-328-3p expression in 88 pairs of osteosarcoma and matched non-cancerous bone tissues were detected by quantitative real-time PCR. Then, the associations of miR-328-3p expression with various clinicopathological features of osteosarcoma patients were statistically analyzed. Cell Counting Kit-8 and scratch-wound healing were performed to evaluate roles of miR-328-3p in human osteosarcoma cells. After that, luciferase reporter assay, western blot analysis and rescue assay were applied to determine the underlying molecular mechanisms of miR-328-3p in osteosarcoma cells. RESULTS: miR-328-3p expression in osteosarcoma tissues was significantly lower than those in non-cancerous bone tissues (P<0.001). miR-328-3p downregulation was significantly associated with advanced surgical stage, positive metastasis and recurrence (all P<0.05). Functionally, enforced expression of miR-328-3p efficiently suppressed cell proliferation and migration in vitro. Moreover, matrix metalloprotease 16 (MMP16) was identified as a direct target of miR-328-3p in osteosarcoma cells. Notably, MMP16 overexpression partially reversed the miR-328-3p-inhibited cell proliferation and migration of osteosarcoma cells. CONCLUSIONS: Our data indicated that the aberrant expression of miR-328-3p may play a crucial role in malignant progression of human osteosarcoma. More importantly, miR-328-3p may function as a tumor suppressor inhibiting osteosarcoma cell proliferation and migration partially mediated by regulating of MMP16. |
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