Abstract

To investigate the role of Zinc finger X-chromosomal protein (ZFX) in oncogenesis of Osteosarcoma tumor. Here, we first conducted an expression analysis of ZFX in Osteosarcoma cell lines. Then, we constructed ZFX-specific small interfering RNA (siRNA)-lentiviral vector that is capable of effectively inhibiting the expression of ZFX gene in human Osteosarcoma Saos-2 cells, and investigated systemically the impacts of ZFX silence on the growth and invasive ability of the cancer cells in vitro. Furthermore, we determined the effects of ZFX knockdown on the cell cycle distribution and apoptosis of Saos-2 cells. We found that ZFX inhibition resulted in significantly impaired proliferation and colony formation as well as mitigated invasiveness of Saos-2 cells. Importantly, si-ZFX infected cells exhibited a greater portion of cells at G1 phase, but a minor portion of S and G2/M phase cells. Moreover, a greater portion of sub-G1 apoptotic cells was observed in si-ZFX infected cells. These results strongly suggest that ZFX is a novel proliferation regulator that promotes growth of Osteosarcoma cells, and downregulation of ZFX expression induces growth suppression of Saos-2 cells via arrested G0/G1 phase cell cycle and apoptosis pathways, thereby indicating that ZFX may serve as a new molecular target for Osteosarcoma tumor therapy.

Highlights

  • Osteosarcoma is an aggressive malignant tumor arising from primitive transformed cells of mesenchymal origin

  • The low viability and colony-forming efficiency of si-Zinc finger X-chromosomal protein (ZFX) infected Saos-2 cells demonstrated that downregulation of ZFX expression inhibits the growth of Osteosarcoma cells in vitro

  • Effects of knock-down of ZFX on cell cycle progression and apoptosis: To determine the potential mechanism underlying the role of ZFX in the growth of Saos-2 cells, the cell cycle profile of si-CTRL and si-ZFX groups were determined by Fluorescence-activated cell sorting (FACS) analysis 96 hours after infection (Fig.4A)

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Summary

Introduction

Osteosarcoma is an aggressive malignant tumor arising from primitive transformed cells of mesenchymal origin. Despite a recent improvement in long-term survival rates, the prognosis of Osteosarcoma is still poor.[1,2] it is necessary to find new therapeutic molecular targets and strategies for the prevention and treatment of Osteosarcoma. It has been established that Osteosarcoma arises as a consequence of the accumulation of multiple genetic alterations involving critical genes that control cell proliferation and mitosis.[3,4] Patients with Osteosarcoma may find that alternative treatment methods are the best option. Many forms of treatment are currently being researched as more is learned about how cancer interacts with the body. Better understanding of genetic carcinogenic effect has led to a new era of targeted therapy in the management of Osteosarcoma.[5]

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