Expression of microRNA-150 and its Target Gene IGF2BP1 in Human Osteosarcoma and their Clinical Implications

microRNA-150及其靶基因IGF2BP1在人类骨肉瘤中的表达及其临床意义

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Abstract

Previous study revealed that microRNA (miR)-150 might function as a tumor suppressor in osteosarcoma partially by targeting Insulin-Like Growth Factor 2 mRNA-Binding Protein 1 (IGF2BP1). The aim of this study was to investigate the clinical significance of miR-150-IGF2BP1 axis in human osteosarcoma which remains unclear. At first, expression levels of miR-150, and IGF2BP1 mRNA and protein in 20 osteosarcoma and matched adjacent noncancerous tissues were respectively detected by quantitative real-time PCR and western blot analyses. Then, subcellular localization and expression pattern of IGF2BP1 protein in 100 osteosarcoma tissues were examined by immunohistochemistry. Associations of miR-150/IGF2BP1 expression with various clinicopathological features and patients' prognosis were also statistically evaluated. As a result, miR-150 expression was significantly decreased, while IGF2BP1 mRNA and protein expression were dramatically increased in osteosarcoma tissues compared to matched adjacent noncancerous tissues (all P < 0.001). Immunostaining of IGF2BP1 protein was localized in cytoplasm of tumor cells in osteosarcoma tissues. Statistically, low miR-150 expression and/or high IGF2BP1 protein immunoreactive score were all significantly associated with high tumor grade, presence of metastasis and recurrence, as well as poor response to chemotherapy (all P < 0.05). Moreover, miR-150, IGF2BP1 and combined miR-150/IGF2BP1 expressions were all identified as independent prognostic factors for overall and disease-free survivals of osteosarcoma patients (all P < 0.05). In conclusion, our data suggest that miR-150 and its downstream target IGF2BP1 may be a crucial axis for the development, progression and patients' prognosis of ostesarcoma. The newly identified miR-150/IGF2BP1 axis might be a novel potential therapeutic target for osteosarcoma treatment.

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