Downregulation of microRNA-217 and microRNA-646 acts as potential predictor biomarkers in progression, metastasis, and unfavorable prognosis of human osteosarcoma

摘要

Despite the progress in therapeutic targets, it remains dissatisfactory for most osteosarcoma patients with metastasis or recurrence osteosarcoma. Therefore, it is required to determine the involved mechanisms of osteosarcoma. The aim of this study was to investigate the expression level of MiR-217 and miR-646 and also their association with clinicopathological features in patients with osteosarcoma. Total RNA was purified from patients with osteosarcoma and non-cancerous bone tissues, and then quantitative real-time PCR was applied to evaluate the expression level of microRNAs. Our result suggested that miR-217 expression was remarkably deceased in osteosarcoma bone tissue when compared with non-cancerous bone tissues (mean +/- SD 5.32 +/- 1.231, 2.01 +/- 0.78; P=0.024) and miR-646 expression decreased in osteosarcoma bone tissue in comparison with normal tissues (mean +/- SD 4.56 +/- 1.45, 1.76 +/- 1.24; P=0.041). Our findings indicated that decreased expression of MiR-217 and miR-646 was strongly correlated with high tumor, node, and metastasis (TNM) stage (P=0.015, P=0.002) and large cancer diameter (P=0.041, P=0.053). Kaplan-Meier survival and log-rank analysis indicated that shorter overall survival was strongly linked to decreased expression of miR-217 and miR-646 (log-rank test P=0.034, P=0.026). In terms of miR-217, multivariate Cox proportional hazards model analysis has showed that reduction of miR-217 expression (P=0.001), TNMstage (P=0.046), and lymph node metastasis (P=0.006) were independently linked to a short-time survival of patients. In terms of miR-646, low expression of miR-646 (P=0.021), TNM stage (P=0.052), and tumor size (P=0.043) were independently associated with poor survival of patients as prognostic factors. Our findings suggested that downregulation of MiR-217 and miR-646 was associated with progression of osteosarcoma. MiR-217 and miR-646 may play a key role in suppression of tumor in osteosarcoma and would be applied as a novel therapeutic agent.