Abstract

von Willebrand factor (vWF) is a major procoagulant molecule that was shown to differentiate between metastatic and primary osteosarcoma (OS) tissues and associated with increased metastasis. However, its functional role in OS progression has been unclear yet. The expression profile of vWF and miR-24 in human OS tissues was characterized using immunofluorescence labeling and quantitative real-time PCR analysis. The interaction between miR-24 and vWF was identified by dual luciferase reporter assay. The effects of vWF and miR-24 on OS cells were assessed by cell proliferation, colony formation, and migration. The clinical significance of miR-24 in OS patients was analyzed using Kaplan–Meier analyses and Pearson’s Chi-squared test. Here, we reported that the expression of vWF was significantly increased, but miR-24 was significantly decreased in OS tissues (n=84). vWF was further validated as the target of miR-24 in MG-63 and U2OS cells. miR-24 obviously suppressed the proliferation and migration of MG-63 and U2OS cells. However, the migration-inhibiting activity of miR-24 was predominantly attenuated by vWF overexpression. Clinically, low miR-24 expression in human OS tissues was significantly associated with tumor metastasis and predicted a poor survival in OS patients. This work demonstrated that vWF, as a downstream effector of miR-24, played an important role in controlling OS cell progression. Target miR-24 or vWF, therefore, promises to be an effective biological target for OS treatment.

Highlights

  • Osteosarcoma (OS) is a malignant bone cancer with high mortality in children and young adults worldwide [1]

  • The expression of von Willebrand factor (vWF) was significantly increased in OS tissues and cell lines To uncover the role of vWF in the progression of OS, the expressions of vWF were analyzed in 84 human OS tissues by immunofluorescence labeling and quantitative real-time PCR analysis

  • Discussion vWF is a mainly expressed in endothelial cell (EC) and megakaryocytes. vWF has important roles in hemostasis through facilitating platelet aggregation [22]

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Summary

Introduction

Osteosarcoma (OS) is a malignant bone cancer with high mortality in children and young adults worldwide [1]. Emerging roles of vWF involved in cancer cell biology, especially in tumor metastasis, were identified in many types of human cancers [4,5,6]. VWF was suggested as the important mediator of platelet–tumor cells interactions, thereby promoting metastasis [6]. This conclusion was further confirmed by the finds that vWF inhibition effectively decreased tumor metastasis in murine and reduced the adhesion of colon cancer cells to endothelial cells (ECs) [7,8]. The functional involvement of vWF in OS and its mechanism remain unknown

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