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.

Geniposide Alleviates Oxidative Stress of Mice With Depression-Like Behaviors by Upregulating Six3os1

“…Previous studies have reported that the Fez family zinc finger protein 1 (Fezf1) serves as an important transcription factor to mediate neurological development (Shimizu et al, 2010;Lan et al, 2018). Furthermore, Fezf1 regulated various cell processes in glioma cells by activating the AKT-ERK signaling pathway (Yu et al, 2018).…”

Potential five‑mRNA signature model for the prediction of prognosis in patients with papillary thyroid carcinoma

“…In addition, the ERFE gene was demonstrated to be associated with OS in colon cancer using univariate Cox regression analysis (39). Of note, the FEZF1 gene is an independent predictive factor for cervical cancer recurrence and promotes cervical cancer cell migration and proliferation (40). Of note, SLC22A31 mRNA expression levels are associated with OS in right-sided colon cancer, as determined using TCGA data (39).…”

FEZF1-AS1: a novel vital oncogenic lncRNA in multiple human malignancies

“…Many years of research have shown that FEZF1 plays a key role in the development of nervous system [14]. Recently, FEZF1 has also been implicated in the progression of tumorigenesis, including enhancing the proliferation and tumorigenicity of GC by binding and activating the oncogene K-ras [15], promoting cell migration and invasion of CRC cells [16], playing a carcinogenic role in CC by acting as a transcriptional activating factor in the Wnt pathway [17], facilitating the development of glioma cells by activating Akt-ERK pathway [18], and so on. Based on the enthusiasm for the study of the FE1 family, there are more and more reports about FEZF1-AS1.…”