Abstract

Osteosarcoma (OS) is the most common primary bone tumor that affects adolescents and young adults. Disruption of microRNA (miRNA) regulation is well established in the pathophysiology of different cancers, including OS. Increased expression of miR-9 in OS positively correlates with the tumor size, clinical stage, and distant metastasis. In the present study, we used two different OS cell lines, MG-63 and Saos-2, as in vitro models. miR-9 inhibitor and miR-9 mimics were used to study the function of miR-9 in these two cell lines. We determined the effect of miR-9 inhibition on cell proliferation, cell cycle, apoptosis, and the protein expression of different genes. Our results demonstrated that miR-9 inhibition in the human OS cell lines suppresses their metastatic potential, as determined by decreased cell proliferation and cell cycle arrest, decreased invasion, and increased apoptosis. The Western blot analysis showed that E-cadherin, matrix metalloproteinase 13, forkhead box O3, Bcl-2-like protein 11, and β-catenin are involved in miR-9 signaling. Moreover, miR-9 mimics rescued the effects caused by the inhibition of miR-9 in the OS cell lines. Our findings suggest that miR-9 is important for mediating OS cell migration, invasion, metastasis, and apoptosis. Inhibition of miR-9 could be further explored as a therapeutic target to treat OS.

Highlights

  • Osteosarcoma (OS) is the most common primary bone tumor that affects adolescents and young adults

  • We showed that proteins such as E-cadherin, matrix metalloproteinases (MMPs)-13, forkhead box O3 (FOXO3a), Bcl2-L-11, and β-catenin are involved in the miR-9 signaling and could be further explored as therapeutic targets to treat OS

  • Using a specific miR-9 inhibitor, the expression of miR-9 was significantly downregulated in both OS cell lines compared to controls (Figure 1A)

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Summary

Introduction

Osteosarcoma (OS) is the most common primary bone tumor that affects adolescents and young adults. Because these tumors have a high metastasis capability, they are considered as the most frequent cause of cancer-related morbidity and mortality. Surgery and chemotherapy are the standard approaches for the treatment of the disease. The prognosis of OS has improved with these standard regimens, the overall survival remains unsatisfactory due to a high metastasis rate [1,2,3]. Despite various efforts of the research community, the mechanism underlying OS development remains unclear.

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