ZWINT Promotes the Proliferation, Migration, and Invasion of Cervical Cancer Cells by Regulating the p53/p21 Signaling Pathway

Abstract

Cervical cancer leads to 300,000 deaths annually and the mechanism of cervical carcinogenesis remains unclear. Zeste White 10-interacting kinetochore protein (ZWINT) is uniquely elevated in malignancies, promoting proliferation, migration, and colony formation of cancer cells. To investigate the role of ZWINT in proliferation, migration, invasion of cervical cancer, and evaluate the potential ability of ZWINT as a therapeutic target. First, ZWINT expression in cervical cancer was analyzed using the bioinformatic methods and assessed in several cervical cancer cell lines. The cell viability and colony formation assays were used to evaluate cell proliferation. Then, transwell assay was performed to investigate cell migration and invasion. Moreover, western blot was used to measure the expression level of ZWINT, matrix metalloproteinase 9 (MMP-9), N-cadherin, E-cadherin, p53 and p21 in CaSki and HeLa cells with ZWINT overexpression or knockdown. The bioinformatic analysis and western blot assay revealed the expression of ZWINT was significantly increased in cervical cancer. The cell viability and colony formation analysis illustrated that cell proliferation could be promoted by ZWINT overexpression and suppressed by ZWINT knockdown. Moreover, ZWINT promoted migration and invasion of CaSki and HeLa cells, through regulating the expression of MMP-9, N-cadherin, and E-cadherin. Furthermore, ZWINT attenuated the expression of p53 and p21 in cervical cancer cells. In summary, ZWINT functions in promoting cell proliferation, migration, and invasion of cervical cancer cells by suppressing p53/p21 signaling pathway, which indicated ZWINT is a potential therapeutic target for cervical cancer treatment.