Increased Expression of microRNA-199b-5p Associates with Poor Prognosis Through Promoting Cell Proliferation, Invasion and Migration Abilities of Human Osteosarcoma.

ABSTRACT

MicroRNA (miR)-199b-5p has been reported to be upregulated in human osteosarcoma tissues and participate in the Notch signaling in osteosarcoma cells. This study was aimed to investigate the associations of miR-199b-5p expression with tumor progression of primary osteosarcoma, and to deepen the understanding of its involvement in carcinogenesis. Quantitative real-time reverse transcriptase-polymerase chain reaction was performed to detect expression levels of miR-199b-5p in 98 osteosarcoma and corresponding adjacent normal tissues. Then, the correlations of its expression with clinicopathological characteristics and patient prognosis were statistically analyzed. Moreover, in vitro assays were performed to assess the effects of miR-199b-5p on the proliferation, migration and invasion of two human osteosarcoma cell lines MG63 and U2OS. Compared to normal controls, miR-199b-5p expression was significantly upregulated in osteosarcoma tissues (P < 0.001). In addition, the expression levels of miR-199b-5p in osteosarcoma patients with high tumor grade (P = 0.008), positive metastasis (P = 0.001) and positive recurrence (P = 0.001) were markedly higher than those with low tumor grade, negative metastasis and negative recurrence. Moreover, osteosarcoma patients with high miR-199b-5p expression showed shorter overall survival (P < .001) and shorter disease-free survival (P < 0.001) than those with low expression. Furthermore, the inhibition of miR-199b-5p significantly suppressed cell proliferation, and reduced the migratory and invasive abilities of osteosarcoma cells. This study offer the convincing evidence for the first time that the increased expression of miR-199b-5p may play crucial roles in aggressive progression and poor prognosis of human osteosarcoma. miR-199b-5p may function as an oncogene by positively regulating the malignant potentials of this neoplasm.