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

Pathol Oncol Res. 2019 Apr;25(2):527-533. doi: 10.1007/s12253-018-0454-0. Epub 2018 Sep 15.

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.

Keywords: Clinicopathological feature; Disease-free survival; Insulin-like growth factor 2 mRNA-binding protein 1; Osteosarcoma; Overall survival; microRNA-150.

MeSH terms

  • Adult
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Bone Neoplasms / genetics
  • Bone Neoplasms / mortality
  • Bone Neoplasms / pathology*
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Osteosarcoma / genetics
  • Osteosarcoma / mortality
  • Osteosarcoma / pathology*
  • RNA-Binding Proteins / biosynthesis*
  • RNA-Binding Proteins / genetics

Substances

  • Biomarkers, Tumor
  • IGF2BP1 protein, human
  • MIRN150 microRNA, human
  • MicroRNAs
  • RNA-Binding Proteins