MiRNA-206 suppresses the metastasis of osteosarcoma via targeting Notch3

Abstract

To investigate the role of microRNA-206 (miRNA-206) in the malignant progression of osteosarcoma and the underlying mechanism, expression pattern of miRNA-206 in osteosarcoma tissues and cell lines was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Correlation between miRNA-206 level and prognosis of osteosarcoma patients was analyzed. Regulatory effects of miRNA-206 on the proliferation and metastasis of U2OS and MG63 cells were evaluated by cell counting kit-8 (CCK-8), Transwell and wound healing assay. Through dual-luciferase reporter gene assay, the target gene of miRNA-206 was verified. A series of rescue experiments were conducted to explore the role of miRNA-206/Notch3 in regulating the malignant progression of osteosarcoma. MiRNA-206 was downregulated in osteosarcoma tissues and cell lines, and its level was correlated to poor prognosis and distant metastasis of osteosarcoma patients. Overexpression of miRNA-206 attenuated the proliferative and metastatic abilities of osteosarcoma cells, and miRNA-206 knockdown obtained the opposite trends. Notch3 was verified to be the target gene of miRNA-206, which was upregulated in osteosarcoma and accelerated osteosarcoma cells to proliferate and metastasize. Finally, rescue experiments showed that Notch3 overexpression partially reversed the regulatory effects of miRNA-206 on cellular behaviors of osteosarcoma cells. MiRNA-206 is downregulated in osteosarcoma. Overexpression of miRNA-206 accelerates osteosarcoma cells to proliferate and metastasize by targeting Notch3, thus accelerating the malignant progression of osteosarcoma.