miR-15a represses cancer cell migration and invasion under conditions of hypoxia by targeting and downregulating Bcl-2 expression in human osteosarcoma cells

摘要

Osteosarcoma is a common, high-risk primary bone malignancy that mostly affects the younger population. There has been no marked improvement in the clinical outcomes of osteosarcoma patients to date, and cancer recurrence and metastasis are common in high-grade osteosarcoma. Therefore, identifying new biomarkers and novel therapeutic targets is crucial for improving the prognosis of osteosarcoma patients. In the present study, the MG63 human osteosarcoma cell line was employed to examine the role of microRNA (miR)-15a in regulating cellular activities under hypoxic conditions. It was demonstrated that hypoxia stimulates migration and invasion in MG63 cells, which was correlated with the downregulation of miR-15a and upregulation of B-cell lymphoma 2 (Bcl-2) expression. Introduction of miR-15a or knockdown of endogenous Bcl-2 may reduce hypoxia-induced cell invasion and migration through the regulation of matrix metalloproteinases. Analysis of the expression of miR-15a indicated that hypoxia repressed the transcription of deleted in lymphocytic leukemia 2 (DLEU2), which is the host gene of miR-15a. These findings indicated that miR-15a may be a valuable target for the treatment of osteosarcoma, particularly for patients with high-grade cancer or heavy tumor burden.