Elevated expression of microRNA-328-3p suppresses aggressive malignant behaviors via targeting matrix metalloprotease 16 in osteosarcoma

Abstract

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.