Ezrin promotes invasion and migration of the MG63 osteosarcoma cell / 中华医学杂志(英文版)

ABSTRACT

<p><b>BACKGROUND</b>Evidence shows that ezrin plays an important role in the development of some human malignancies. But the mechanism by which ezrin may affect tumor cell invasion and metastasis remains unclear.</p><p><b>METHODS</b>In this study, the expression of ezrin was verified in osteosarcoma (OS) cells and tissues by comparison with normal bone cells and tissues using Western blotting. OS-MG63 were transfected with pcDNA3.1-ezrin or pGenesil-1/shRNA-ezrin and the stably transfected cells were selected with G418 to yield the ezrin cell line. The OS-MG63 tumor cells were delivered by tail vein to female BALB/c to develop pulmonary metastasis model in vivo. Ezrin was identified as a direct target of miR-183 via a luciferase reporter carrying the 3'-untranslated region of ezrin. Migration assays and invasion assays were done with the transwells. Signaling pathway was studied by Western blotting and/or inhibitor.</p><p><b>RESULTS</b>Ectopic overexpression of ezrin in OS cell line MG63 promoted tumor cell invasion and migration. Consistent with this, knockdown of ezrin inhibited tumor cell invasion and migration. Similar results were obtained in the experimental metastasis model in vivo. We identified ezrin as a direct target of miR-183. What is more, ectopic expression of ezrin could induce the expression of N-cadherin and enhance the activity of extracellular signal-regulated kinase (ERK) signaling.</p><p><b>CONCLUSION</b>Collectively, these results suggest that ezrin as a direct target of miR-183 promotes the aggressiveness of OS via increased N-cadherin and activating ERK signaling.</p>