Abstract
BackgroundIn humans, sex-determining region-Y (SRY) related high-mobility-group box 4 (SOX4) is linked to development and tumorigenesis. SOX4 is over-expressed in several cancers and has prognostic significance. This study evaluated whether SOX4 affects oncogenic behavior and chemoradiotherapy response in head and neck squamous cell carcinoma (HNSCC) cells, and documented the relationship between its expression and prognosis in oral squamous cell carcinoma (OSCC).MethodsWe used small interfering RNA in HNSCC cells to evaluate the effect of SOX4 on cell proliferation, apoptosis, chemoradiation-induced apoptosis, invasion, and migration. SOX4 expression in OSCC tissues was investigated by immunohistochemistry.ResultsSOX4 knockdown (KO) decreased cell proliferation and induced apoptosis by activating caspases-3 and −7, and poly-ADP ribose polymerase and suppressing X-linked inhibitor of apoptosis protein in HNSCC cells; it also enhanced radiation/cisplatin-induced apoptosis; and suppressed tumor cell invasion and migration. Immunostaining showed SOX4 protein was significantly increased in OSCC tissues compared with adjacent normal mucosa. SOX4 expression was observed in 51.8 % of 85 OSCC tissues, and was significantly correlated with treatment failure (P = 0.032) and shorter overall survival (P = 0.036) in patients with OSCC.ConclusionsSOX4 may contribute to oncogenic phenotypes of HNSCC cells by promoting cell survival and causing chemoradioresistance. It could be a potential prognostic marker for OSCC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1875-8) contains supplementary material, which is available to authorized users.
Highlights
In humans, sex-determining region-Y (SRY) related high-mobility-group box 4 (SOX4) is linked to development and tumorigenesis
We investigated whether SOX4 affects tumor cell behaviors such as cell proliferation, apoptosis, invasion, migration, and chemoradiation-induced apoptosis in head and neck squamous cell carcinoma (HNSCC) cells to validate its potential as a novel molecular target
SOX4 knockdown (SOX4-KO) suppresses tumorigenic activities in HNSCC cells Initially, SOX4 expression at mRNA and protein levels was evaluated in HNSCC cells and HaCaT cells
Summary
Sex-determining region-Y (SRY) related high-mobility-group box 4 (SOX4) is linked to development and tumorigenesis. This study evaluated whether SOX4 affects oncogenic behavior and chemoradiotherapy response in head and neck squamous cell carcinoma (HNSCC) cells, and documented the relationship between its expression and prognosis in oral squamous cell carcinoma (OSCC). Squamous cell carcinomas represent about 90 % of oral cavity cancer. Oral squamous cell carcinoma (OSCC) is the sixth most prevalent malignancy worldwide and the third most common cancer in developing nations [1]. The sex-determining region Y (SRY) related high-mobility-group (HMG) box family— called the SOX family—includes 20 highly conserved transcription factors that affect diverse developmental processes [3]. SOX4 expression results in alterations of oncogenic phenotypes, including inhibition of apoptosis, cell-cycle progression and irradiation-induced apoptosis, and promotion of epithelial to mesenchymal transition in a variety of cancer
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