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Y染色体性别决定区盒蛋白3通过转录激活Snail1诱导骨肉瘤细胞发生上皮-间质转化。

Sex-determining region Y-box protein 3 induces epithelial-mesenchymal transition in osteosarcoma cells via transcriptional activation of Snail1.

作者信息

Qiu Manle, Chen Daoyun, Shen Chaoyong, Shen Ji, Zhao Huakun, He Yaohua

机构信息

Department of Sports Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.

Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.

出版信息

J Exp Clin Cancer Res. 2017 Mar 23;36(1):46. doi: 10.1186/s13046-017-0515-3.

DOI:10.1186/s13046-017-0515-3
PMID:28335789
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5364714/
Abstract

BACKGROUND

The transcription factor sex-determining region Y-box protein 3 (SOX3) plays important roles in various types of cancer. However, its expression and function have not yet been elucidated in osteosarcoma (OS).

METHODS

The expression levels of SOX3 in OS tissues and OS cell lines were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. The effects of SOX3 expression on OS cell biological traits were investigated by overexpressing and downregulating SOX3 protein. The expression of epithelial-mesenchymal transition (EMT) markers and transcription factors associated with EMT (EMT-TFs), were detected simultaneously. The mechanism underlying SOX3-mediated Snail1 expression was further investigated.

RESULTS

SOX3 was upregulated in human OS tissues. SOX3 overexpression promoted the EMT, migration and invasion in OS cells. The downregulation of SOX3 resulted in opposing effects. Furthermore, SOX3 upregulation enhanced the expression of the transcriptional repressor Snail1 by binding to its promoter region. Additionally, a positive correlation among the expression of SOX3, Snail1, and E-cadherin was demonstrated in human OS tissues.

CONCLUSIONS

SOX3 promotes migration, invasiveness, and EMT in OS cells via transcriptional activation of Snail1 expression, suggesting that SOX3 is a novel regulator of EMT in OS and may serve as a therapeutic target for the treatment of OS metastasis.

摘要

背景

转录因子性别决定区Y盒蛋白3（SOX3）在多种癌症中发挥重要作用。然而，其在骨肉瘤（OS）中的表达和功能尚未阐明。

方法

通过定量实时聚合酶链反应（qRT-PCR）和蛋白质免疫印迹分析确定SOX3在OS组织和OS细胞系中的表达水平。通过过表达和下调SOX3蛋白来研究SOX3表达对OS细胞生物学特性的影响。同时检测上皮-间质转化（EMT）标志物及与EMT相关的转录因子（EMT-TFs）的表达。进一步研究SOX3介导Snail1表达的机制。

结果

SOX3在人OS组织中上调。SOX3过表达促进OS细胞的EMT、迁移和侵袭。SOX3下调则产生相反的效果。此外，SOX3上调通过结合其启动子区域增强转录抑制因子Snail1的表达。另外，在人OS组织中，SOX3、Snail1和E-钙黏蛋白的表达之间呈正相关。

结论

SOX3通过转录激活Snail1表达促进OS细胞的迁移、侵袭和EMT，提示SOX3是OS中EMT的新型调节因子，可能成为治疗OS转移的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15a8/5364714/349429d282ab/13046_2017_515_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15a8/5364714/69d3333d849a/13046_2017_515_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15a8/5364714/f50005e0df2b/13046_2017_515_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15a8/5364714/67b4068827c1/13046_2017_515_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15a8/5364714/90ee2078f53a/13046_2017_515_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15a8/5364714/7631390675eb/13046_2017_515_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15a8/5364714/349429d282ab/13046_2017_515_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15a8/5364714/69d3333d849a/13046_2017_515_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15a8/5364714/f50005e0df2b/13046_2017_515_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15a8/5364714/67b4068827c1/13046_2017_515_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15a8/5364714/90ee2078f53a/13046_2017_515_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15a8/5364714/7631390675eb/13046_2017_515_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15a8/5364714/349429d282ab/13046_2017_515_Fig6_HTML.jpg

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