miR-125b suppresses the proliferation and migration of osteosarcoma cells through down-regulation of STAT3
miR-125b suppresses the proliferation and migration of osteosarcoma cells through down-regulation of STAT3
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DOI：
10.1016/j.bbrc.2011.10.117
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发表时间：
2011-12-09
影响因子：
3.1
通讯作者：
Xiao, Tao
中科院分区：
文献类型：
--
作者：
Liu, Li-hong;Li, Hui;Xiao, Tao
越来越多的证据表明，microrna参与了肿瘤发生发展的多个过程。发现异常表达的miR-125b在几种类型的癌症中发挥基础性作用；然而，miR-125b是否参与调控骨肉瘤的发生和发展尚不清楚。在这里，我们证明miR-125b在骨肉瘤样本和人骨肉瘤细胞系中经常下调。异位恢复人骨肉瘤细胞中miR-125b的表达，在体外抑制增殖和迁移，在体内抑制肿瘤形成。我们进一步确定了信号换能器和转录激活器3 （STAT3）是miR-125b的直接和功能性下游靶标。有趣的是，我们发现miR-125b的表达在转录水平上受到STAT3的调控。STAT3在体外结合miR-125b的启动子区域，并作为反激活子。综上所述，我们的研究结果指出了miR-125b在骨肉瘤分子病因学中的重要作用，并提示miR-125b是骨肉瘤治疗的潜在靶点。(C) 2011爱思唯尔公司版权所有。
There is accumulating evidence that microRNAs are involved in multiple processes in development and tumor progression. Abnormally expressed miR-125b was found to play a fundamental role in several types of cancer; however, whether miR-125b participates in regulating the initiation and progress of osteosarcoma still remains unclear. Here we demonstrate that miR-125b is frequently down-regulated in osteosarcoma samples and human osteosarcoma cell lines. The ectopic restoration of miR-125b expression in human osteosarcoma cells suppresses proliferation and migration in vitro and inhibits tumor formation in vivo. We further identified signal transducer and activator of transcription 3 (STAT3) as the direct and functional downstream target of miR-125b. Interestingly, we discovered that the expression of miR-125b is regulated by STAT3 at the level of transcription. STAT3 binds to the promoter region of miR-125b in vitro and serves as a transactivator. Taken together, our findings point to an important role in the molecular etiology of osteosarcoma and suggest that miR-125b is a potential target in the treatment of osteosarcoma. (C) 2011 Elsevier Inc. All rights reserved.