FEZF1 is an Independent Predictive Factor for Recurrence and Promotes Cell Proliferation and Migration in Cervical Cancer

Abstract

The Fez family zinc finger protein 1 (FEZF1), a critical transcription factor in nervous system development, has been implicated in cancer progression recently. However, its clinical significance remains unknown. By analyzing gene expression data of eight most common cancer types from The Cancer Genome Atlas (TCGA), we found that FEZF1 prominently associated with the recurrence-free survival of cervical cancer patients ( P<0.001) and was an independent diagnostic factor for cervical cancer recurrence ( P=0.002). Moreover, FEZF1 expression was significantly higher in the tumor samples from cervical cancer patients with relapse in TCGA( P=0.015). By RNA interference, we knocked down FEZF1 and found that cell proliferation, growth and migration were significantly decreased in C33A and SiHa cells. Meanwhile, FEZF1 knockdown also attenuated the growth of C33A cells in nude mice. In contrast, expression of FEZF1 promoted cell proliferation, growth and migration in HeLa cells. Using chromatin immunoprecipitation (ChIP) assay, we revealed that FEZF1 could bind to multiple key genes in the Wnt signaling pathway in HeLa cells. Furthermore, analysis of the levels of β-catenin protein, the core component of the Wnt pathway, and downstream effector genes of the pathway showed that FEZF1 could activate the Wnt pathway. Together, these results suggest that FEZF1 promotes cell proliferation and migration possibly by acting as a transcriptional activator of the Wnt signaling pathway in cervical cancer, and also provide a valuable molecular predictive marker for cervical cancer recurrence.