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

Lei Wang,Ailixiati Aireti,Kun Li,Aizezi Aihaiti

doi:10.1007/s12253-018-0454-0

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.

Highlights

Osteosarcoma is the most common type of bone tumor among children, adolescents, and young adults worldwide, representing a leading cause of cancer-related death [1]
Differences of miR-150, Insulin-Like Growth Factor 2 mRNA-Binding Protein 1 (IGF2BP1) mRNA and protein expression between osteosarcoma and the corresponding noncancerous bone tissues were evaluated by the paired t test
The expression level of miR-150 in osteosarcoma tissues was significantly lower than that in adjacent noncancerous tissues, while the expression levels of IGF2BP1 mRNA and protein were both markedly increased in osteosarcoma tissues

Summary

Introduction

Osteosarcoma is the most common type of bone tumor among children, adolescents, and young adults worldwide, representing a leading cause of cancer-related death [1]. In osteosarcoma, Li et al [13] in 2015 reported that miR-150 inhibited cell proliferation, invasion, and metastasis, while stimulated cell apoptosis in osteosarcoma; Zhan et al [14] in 2016 indicated that miR-150 upregulation could reduce osteosarcoma cell invasion and metastasis; Wang et al [15] found that miR-150 expression level was lower in human osteosarcoma cell lines compared to the normal osteoblast cell line, which showed statistical significance (P < 0.01), and enforced expression of this miRNA might inhibit proliferation in human osteosarcoma cell lines; In the same year, Qu et al [16] confirmed Insulin-Like Growth Factor 2 mRNA-Binding Protein 1 (IGF2BP1) as a direct target of miR-150, which could suppress cell proliferation, migration, and invasion, and induce apoptosis in vitro as well as suppressed tumor growth of osteosarcoma in vivo These findings suggest that miR-150-IGF2BP1 axis may play potential roles in regulating osteosarcoma progression.

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