Anti-Silencing Function 1B Overexpression Affects Prognosis and Promotes Invasion in Cervical Carcinoma via Activation of Wnt/β-Catenin Signaling Pathway
Abstract Background: Anti-silencing function 1B histone chaperone (ASF1B) has been identified to compensate for growth defects and sensitivity to replication stress. Recent studies demonstrated that ASF1B plays an important role in the tumorigenesis of human cancer. However, its relationship with clinical outcome of cervical carcinoma is unknown. Therefore, we aimed to investigate the expression pattern and clinical significance of ASF1B in cervical cancer and its role in regulating invasion and metastasis of cervical cancer cell lines.Methods: Expression of ASF1B was analyzed in eight cervical cancer cell lines, and eight pairs of cervical cancer samples and the adjacent normal specimens, using real-time PCR and western blotting. Immunohistochemistry was used to analyze ASF1B expression in paraffin-embedded tissues from 147 cervical cancer patients. The association between ASF1B expression levels, clinicopathological parameters, and prognosis was analyzed statistically. Moreover, the biological function and potential mechanism of ASF1B in migration and invasion of cervical cancer cells were investigated by in vitro experiments and Western blotting.Results: ASF1B mRNA and protein levels were overexpressed in cervical cancer cell lines and tissues compared with normal cells and adjacent normal cervical specimens. In paraffin-embedded cervical carcinoma tissues, upregulation of ASF1B protein was identified in 86 (58.5%) of 147 cases, and was remarkably associated with pelvic lymph node metastasis, lymphovascular space involvement, property of surgical margin, FIGO stage, sqaumous cell carcinoma antigen and poor survival. Cox analysis demonstrated that ASF1B expression was an independent risk predictor for survival in patients with cervical carcinoma. Additionally, down-regulation of ASF1B significantly inhibited invasion and migration of cervical cancer cells. Moreover, it was demonstrated that ASF1B regulated the Wnt/β-catenin pathway in cervical carcinoma.Conclusions: This study suggested that ASF1B might serve as a important prognostic biomarker and therapeutic target for patients with cervical carcinoma.