Abstract
AbstactSOX2 is a transcription factor that contributes to transcription modification and cancer, but the mechanism by which SOX2 regulates nasopharyngeal carcinoma cell proliferation is not well understood. Here, we identify a SOX2 signaling pathway that facilitates nasopharyngeal carcinoma, where it is upregulated. SOX2 expression was associated with nasopharyngeal carcinoma patient survival. SOX2 knockdown inhibited cell proliferation, colony formation, and tumorigenesis in an subcutaneous mouse xenograft model system. Six hundred and ninety-nine candidate SOX2 downstream dysregulated genes were identified in nasopharyngeal carcinoma cells through cDNA microarray analysis. SOX2 recruited the nuclear transcription factor KLF4 to bind to the PIK3CA promoter upregulate PIK3CA expression, acting to enhance PI3K/AKT signaling and tumorigenesis by upregulating PIK3CA expression. Besides, overexpressing activated AKT or PIK3CA rescued the growth inhibition of cells due to SOX2 knockdown. Together, our study suggest that SOX2 exhibits oncogenic properties and may be a reliable molecular biomarker in nasopharyngeal carcinoma. Targeting SOX2 might be a promising treatment strategy for nasopharyngeal carcinoma treatment.
Highlights
Nasopharyngeal carcinoma, a most commonly diagnosed cancer originating from the epithelial lining of the nasopharynx, has remained high incidence rate in endemic regions, especially in southern China, northern Africa, and Alaska[1]
We found Sex determining region Y-box 2 gene (SOX2) expression was markedly overexpressed in nasopharyngeal carcinoma cell lines compared with NP69 cells (Fig. 2a), suggesting that higher SOX2 expression may be associated with nasopharyngeal carcinoma phenotype
Discussion the mortality rate of nasopharyngeal carcinoma has been decreasing continuously due to advancement in diagnosis and treatment, nasopharyngeal carcinoma is still one of the most lethal primary malignant head and neck tumor in adults, largely because of limited knowledge of precise molecular pathogenesis and paucity of targeted therapies
Summary
Nasopharyngeal carcinoma, a most commonly diagnosed cancer originating from the epithelial lining of the nasopharynx, has remained high incidence rate in endemic regions, especially in southern China, northern Africa, and Alaska[1]. Accumulating evidence from human and animal studies suggests that genetic factors, environmental factors, and the Epstein-Barr virus (EBV) infection have played critical roles in nasopharyngeal carcinoma progression[2,3,4,5]. A growing body of evidence has implicated that transcription factors are involved in tumorigenesis through regulating the abnormal expression of tumor-related genes. Sex determining region Y-box 2 gene (SOX2), located at chromosome 3q26.33, encodes a transcription factor which contains a high mobility group DNA-binding domain in its structure[7].
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