Expression and clinical prognostic role of ZWINT in glioma: Analysis based on data-mining and integration of gene databases

Abstract

Background: Human ZW10 interacting kinetochore protein (ZWINT) gene plays critical roles in mitotic cycle maintenance and is known to be linked with poor clinical prognosis in various tumors. However, the clinical significance of ZWINT in glioma has not yet been understood. The purpose of this study was to determine the expression profile and functions of ZWINT in glioma, to confirm its prognostic value. Methods: The gene expression and clinical information profile were downloaded from The Cancer Genome Atlas (TCGA) dataset and a statistical analysis was made. We probed the edgeR and gplots packages in the R language to identify differentially expressed genes (DEGs). The Kaplan-Meier plotter online tool was used to study the association of ZWINT expression and overall survival (OS) of glioma patients. Immunohistochemistry (IHC) and quantitative RT-PCR were performed to evaluate protein and mRNA expression levels of ZWINT. ZWINT-siRNA was transfected into U251 and U87 glioma cells to inhibit the expression of ZWINT. Then, the effects of ZWINT silencing on glioma cell lines proliferation, invasion and apoptosis were determined by the Celigo assay, MTT assay, transwell assay, Annexin V FACS assay and Caspase-3/7 assay in vitro. Functional and pathway enrichment analysis were performed for DEGs using the DAVID database. Protein-protein interaction (PPI) network analysis was established by STRING and visualized by Cytoscape. Results: Integrated analysis revealed that ZWINT protein and mRNA expression were significantly upregulated in glioma versus normal tissues, its expression was positively correlated with the patient age, poor pathological grade, and conferred poor prognosis. Knockdown of ZWINT expression inhibited the proliferation and invasion of U251 and U87 cells, and apoptosis was distinctly increased following ZWINT-siRNA infection. 20 hub genes and a significant module showed that the DEGs were principally related to cell division, and mitotic cell cycle. Conclusions: Our preliminary study highlighted that the expression of ZWINT is upregulated in glioma, which is correlated with poor prognosis. ZWINT silencing can effectively inhibit proliferation, induce apoptosis and suppress migration and invasion during human glioma development, which may provide a new promising tumorspecific therapeutic combination hub genes target for anti-mitosis agents.