Hypoxia stimulates the migration and invasion of osteosarcoma via up-regulating the NUSAP1 expression.

Ling Zhang,Yang Chen,Donghong Sun,Jingtao Song,Huiting Huang,Xu Xin,Tao Zhang,Yiming Zhang

doi:10.1515/med-2020-0180

Abstract

Osteosarcoma is a highly aggressive malignant tumor, which most commonly occurs in children and adolescents. This study aims to reveal that hypoxia promotes the invasion of osteosarcoma cells by up-regulating the expression of NUSAP1. The expression of HIF-1α and NUSAP1 was significantly up-regulated in MG63 cells cultured in hypoxia for 6–36 h. Furthermore, hypoxia induced the migration and invasion of MG63 cells and regulated the level of E-cad, N-cad, Vimentin, Snail, Slug, MMP2, and MMP9 proteins. Importantly, knockdown of NUSAP1 inhibited hypoxia-induced cell migration and invasion. In the hypoxia microenvironment, the addition of HIF-1α inhibitor or the transfection of siRNA specifically targeting HIF-1α significantly reduced the expression of HIF-1α and NUSAP1 and markedly inhibited the migration and invasion of MG63 cells under the hypoxia microenvironment. In conclusion, hypoxia induced the expression of NUSAP1 in a HIF-1α-dependent manner, stimulating the migration and invasion of MG63 cells.

Highlights

Osteosarcoma is a highly aggressive malignant tumor, which most commonly occurs in children and adolescents
We found that hypoxia induced the expression of Nucleolar and spindle-associated protein 1 (NUSAP1), thereby stimulating the migration and invasion of MG63 cells
We found that the expression of MMP2 and MMP9 significantly increased under the hypoxia microenvironment (Figure 1d, P < 0.05)

Summary

Introduction

Abstract: Osteosarcoma is a highly aggressive malignant tumor, which most commonly occurs in children and adolescents. This study aims to reveal that hypoxia promotes the invasion of osteosarcoma cells by up-regulating the expression of NUSAP1. The expression of HIF-1α and NUSAP1 was significantly up-regulated in MG63 cells cultured in hypoxia for 6–36 h. Hypoxia induced the migration and invasion of MG63 cells and regulated the level of E-cad, N-cad, Vimentin, Snail, Slug, MMP2, and MMP9 proteins. Knockdown of NUSAP1 inhibited hypoxia-induced cell migration and invasion. The addition of HIF-1α inhibitor or the transfection of siRNA targeting HIF-1α significantly reduced the expression of HIF-1α and NUSAP1 and markedly inhibited the migration and invasion of MG63 cells under the hypoxia microenvironment. Hypoxia induced the expression of NUSAP1 in a HIF-1αdependent manner, stimulating the migration and invasion of MG63 cells

Objectives

Methods

Results

Conclusion