Upregulation of micro-ribonucleic acid-128 cooperating with downregulation of PTEN confers metastatic potential and unfavorable prognosis in patients with primary osteosarcoma.

ABSTRACT

OBJECTIVE: Abnormal expression of micro-ribonucleic acid (miRNA [miR])-128 has been observed in various human cancer types, and its validated target genes are implicated in cancer-related cellular processes, such as cell proliferation, differentiation, and apoptosis. Especially, it has been demonstrated that miR-128 may play an important role in the proliferation of human osteosarcoma cells in vitro by directly inhibiting PTEN, which functions as a tumor suppressor in this malignancy. In the current study, we investigated the involvement of miR-128 and its target gene PTEN in tumor progression and prognosis in patients with primary osteosarcoma. MATERIALS AND METHODS: Expression levels of miR-128 and PTEN messenger RNA in osteosarcoma and noncancerous bone tissues obtained from 100 patients with primary osteosarcoma were detected by quantitative real-time polymerase chain reaction. RESULTS: Expression levels of miR-128 and PTEN messenger RNA in osteosarcoma tissues were significantly higher and lower, respectively, than those in noncancerous bone tissues (both P<0.001). In addition, high miR-128 expression and low PTEN expression, alone (miR-128-high or PTEN-low) or combined (miR-128-high/PTEN-low), were all dramatically associated with poor response to chemotherapy and positive metastasis. More importantly, the associations of miR-128-high/PTEN-low expression with these clinicopathological parameters were more significant than miR-128-high or PTEN-low alone. Finally, miR-128 expression, PTEN expression, miR-128/PTEN expression, the response to chemotherapy and the metastatic status were all identified as independent prognostic factors for overall survival and disease-free survival. CONCLUSION: These findings indicate for the first time that the deregulation of miR-128 and its target gene PTEN may be involved in the aggressive progression of human osteosarcoma. Notably, the upregulation of miR-128 cooperating with the downregulation of PTEN may confer an unfavorable prognosis in patients with this malignancy.