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Int. J. Mol. Sci. 2014, 15(1), 423-437; doi:10.3390/ijms15010423

miR-126 Functions as a Tumor Suppressor in Osteosarcoma by Targeting Sox2

Department of Orthopedic Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, China These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 7 October 2013 / Revised: 28 November 2013 / Accepted: 2 December 2013 / Published: 31 December 2013
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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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 osteosarcoma; miR-126; tumor suppressor; sex-determining region Y-box 2
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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.

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