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

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

doi:10.1186/s13046-017-0515-3

Abstract

BackgroundThe 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).MethodsThe 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.ResultsSOX3 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.ConclusionsSOX3 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.

Highlights

The transcription factor sex-determining region Y-box protein 3 (SOX3) plays important roles in various types of cancer
SOX3 is upregulated in human OS tissues We first determined the SOX3 mRNA and protein levels in 42 cases of human OS tissues and in adjacent nontumor samples by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis
The SOX3 mRNA level was assessed in OS tissues and bone cysts (Fig. 1c)

Summary

Introduction

The transcription factor sex-determining region Y-box protein 3 (SOX3) plays important roles in various types of cancer. Osteosarcoma (OS) is one of the most prevalent malignant bone tumors in childhood and adolescence. Epithelial to mesenchymal transition (EMT), a developmental process in which epithelial cells lose polarity and develop a mesenchymal phenotype, plays an important role in the initiation of metastasis [5]. The complex genetic changes during EMT are, at least in part, mediated by a number of specific transcription factors, such as Snail, Slug, Twist, ZEB1, and ZEB2 [7,8,9]. Snail is overexpressed in various human solid tumors, including numerous types of carcinomas, as well as sarcomas, gliomas, neuroblastomas, and melanomas [10, 11].

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