miR-126通过对骨肉瘤中Sox2的作用发挥其肿瘤抑制因子的作用
miR-126 Functions as a Tumor Suppressor in Osteosarcoma by Targeting Sox2
骨肉瘤作为青少年及成人最为常见的骨恶性肿瘤,其早期并无特异性症状及体征,较难早期诊断,这一难题一直困扰着我们。随着对微小RNA的深入研究,也许骨肉瘤的早期诊断与治疗也会迎刃而解。越来越多的研究表明微小RNA-126在骨肉瘤中有表达。通过实时定量PCR,我们发现在32个骨肉瘤组织及4个骨肉瘤细胞系中,miR-126其表达较正常对照组(正常组织及正常成骨细胞系)低。因此,我们尝试在MG-63细胞中高表达miR-126。我们发现过表达miR-126可以抑制细胞增殖及迁徙,进而导致MG-63细胞的凋亡。通过生物信息学预测,我们发现Sox2可能是miR-126的靶基因。通过mRNA、蛋白、荧光素酶分析等实验验证,我们发现恢复Sox2的表达可以阻止由miR-126介导的肿瘤抑制。因此,我们的数据表明miR-126可作为一种有效的肿瘤抑制因子,其可通过抑制Sox2的表达发挥其抑制肿瘤的作用。????
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.
马颜、侯春影、王德伟、徐孝岩、张云奇、毕郑刚、张鹤鹏、耿硕、杨成林
肿瘤学基础医学分子生物学
外科学骨肉瘤miR-126肿瘤抑制因子性别决定区Y框蛋白2
SurgeryOsteosarcomamiR-126tumor suppressorsex-determining region Y-box 2
马颜,侯春影,王德伟,徐孝岩,张云奇,毕郑刚,张鹤鹏,耿硕,杨成林.miR-126通过对骨肉瘤中Sox2的作用发挥其肿瘤抑制因子的作用[EB/OL].(2013-12-20)[2025-08-22].http://www.paper.edu.cn/releasepaper/content/201312-622.点此复制
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