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

International Journal of Molecular Sciences

Chenglin Yang¹  Chunying Hou¹  Hepeng Zhang²  Dewei Wang²  Yan Ma²  Yunqi Zhang²  Xiaoyan Xu²  Zhenggang Bi² 

[1] Department of Orthopedic Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, China;

关键词: osteosarcoma;    miR-126;    tumor suppressor;    sex-determining region Y-box 2;   

DOI  :  10.3390/ijms15010423

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland