ZIC5 promotes aggressiveness and cancer stemness in cervical squamous cell carcinoma

Abstract

Background: Cervical cancer is one of the major malignancies causing morbidity and mortality in women in developing countries. ZIC5 has been found to be associated with a variety of cancers, yet the expression and molecular function of ZIC5 in cervical squamous cell carcinoma (CESC) is unknown.

Methods: We examined the expression of ZIC5 in tumors and normal tissues of CESC patients using immunohistochemistry, immunoblotting and fluorescent quantitative PCR, and used statistical methods to explore its relationship with clinical manifestations. Next, we constructed ZIC5 knockdown and overexpression CESC cell lines to observe the effect of ZIC5 on the proliferation and metastasis of CESC cells. Finally, we applied a nude mouse xenograft tumor model to observe the effect of ZIC5 on tumorigenesis in vivo.

Results: Our results showed that the expression of ZIC5 was higher in cancer tissues than in normal tissues. Prognostic analysis showed that ZIC5 expression level was an independent prognostic factor in CESC patients, and the results of Transwell, CCK-8 and wound healing assays confirmed that overexpression of ZIC5 could promote the proliferation and migration of CESC cells. A nude mouse xenograft tumor model showed that knockdown of ZIC5 inhibited tumor growth in vivo. Database, immunoblotting assay and in vitro sphere-forming assay confirmed that ZIC5 could promote the stemness of CESC cells.

Conclusion: ZIC5 is a factor that indicates a poor prognosis of CESC patients and promotes stemness in CESC cells. ZIC5 may be a potential biomarker and therapeutic target for CESC patients.

Keywords: Aggressiveness; Cancer stemness; Cervical squamous cell carcinoma; Prognosis; ZIC5.