Aberrantly elevated Bmi1 promotes cervical cancer tumorigenicity and tumor sphere formation via enhanced transcriptional regulation of Sox2 genes.

Abstract

The exact molecular mechanisms underlying cervical tumorigenesis are poorly understood. Polycomb complex protein Bmi1 (Bmi1) is involved in the malignant transformation and biological aggressiveness of several human carcinomas. Therefore, the present study assessed the expression of Bmi1 protein in human cervical cancer tissues and examined the mechanisms involved in cervical carcinogenesis. The expression of Bmi1 protein was examined by immunohistochemistry in cervical carcinoma tissues (n=71), high-grade squamous intraepithelial lesions (n=41) and normal cervical tissues (n=47). Expression of Bmi1 protein gradually increased across samples from the normal cervix (1/47; 2.12%), high-grade squamous intraepithelial lesions (5/42; 16.13%) and cervical carcinomas (31/71; 43.66%; P<0.05). Additionally, Bmi1 protein expression was associated with tumor histopathological grade. The effects of Bmi1 silencing and overexpression on tumor sphere formation and the tumorigenicity of cervical cancer cells were investigated. Overexpression of Bmi1 resulted in significantly attenuated tumor formation and tumor sphere formation. Consistently, Bmi1 silencing significantly inhibited tumor formation and tumor sphere formation. Furthermore, Bmi1 upregulated the expression of Sox2, and the dual-luciferase reporter assay and chromatin immunoprecipitation showed that Bmi1 transactivated Sox2 by binding to the two E-box motifs in the Sox2 promoter. In conclusion, aberrantly elevated Bmi1 promotes cervical cancer tumorigenicity and tumor sphere formation via enhanced transcriptional regulation of Sox2 genes as a potential oncogenic factor that participates in the carcinogenesis of cervical carcinomas.