Abstract: Osteosarcoma (OS) is the most common malignant bone tumor in children and young adults, the early symptoms and signs of which are non-specific. The discovery of microRNAs (miRNAs) provides a new avenue for the early diagnosis and treatment of OS. miR-126 has been reported to be highly expressed in vascularized tissues, and is recently widely studied in cancers. Herein, we explored the expression and significance of miR-126 in OS. Using TaqMan RT-PCR analysis, we analyzed the expression of miR-126 in 32 paired OS tumor tissues and 4 OS cell lines and found that miR-126 was consistently under-expressed in OS tissues and cell lines compared with normal bone tissues and normal osteoblast cells (NHOst), respectively. As miR-126 is significantly decreased in OS tissues and cell lines, we sought to compensate for its loss through exogenous transfection into MG-63 cells with a miR-126 mimic. Ectopic expression of miR-126 inhibited cell proliferation, migration and invasion, and induced apoptosis of MG-63 cells. Moreover, bioinformatic prediction suggested that the sex-determining region Y-box 2 (Sox2) is a target gene of miR-126. Using mRNA and protein expression analysis, luciferase assays and rescue assays, we demonstrate that restored expression of Sox2 dampened miR-126-mediated suppression of tumor progression, which suggests the important role of miR-126/Sox2 interaction in tumor progression. Taken together, our data indicate that miR-126 functions as a tumor suppressor in OS, which exerts its activity by suppressing the expression of Sox2.
Keywords: osteosarcoma; miR-126; tumor suppressor; sex-determining region Y-box 2
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Yang, C.; Hou, C.; Zhang, H.; Wang, D.; Ma, Y.; Zhang, Y.; Xu, X.; Bi, Z.; Geng, S. miR-126 Functions as a Tumor Suppressor in Osteosarcoma by Targeting Sox2. Int. J. Mol. Sci. 2014, 15, 423-437.
Yang C, Hou C, Zhang H, Wang D, Ma Y, Zhang Y, Xu X, Bi Z, Geng S. miR-126 Functions as a Tumor Suppressor in Osteosarcoma by Targeting Sox2. International Journal of Molecular Sciences. 2014; 15(1):423-437.
Yang, Chenglin; Hou, Chunying; Zhang, Hepeng; Wang, Dewei; Ma, Yan; Zhang, Yunqi; Xu, Xiaoyan; Bi, Zhenggang; Geng, Shuo. 2014. "miR-126 Functions as a Tumor Suppressor in Osteosarcoma by Targeting Sox2." Int. J. Mol. Sci. 15, no. 1: 423-437.