ZWINT: A potential therapeutic biomarker in patients with glioblastoma correlates with cell proliferation and invasion

Abstract

Glioblastoma (GBM) is the most aggressive primary intracranial tumor in adults. Chemoradiotherapy resistance and recurrence after surgery are the main malignant progression factors, leading to a high mortality rate. Therefore, the exploration of novel biomarkers and molecular mechanisms of GBM is urgent. Differentially expressed genes (DEGs) of GBM were screened in a TCGA dataset. Homo sapiens ZW10 interacting kinetochore protein (ZWINT) was found to be upregulated in GBM, which was confirmed by immunohistochemical staining of a tissue microarray. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. A protein-protein interaction (PPI) network was established by the STRING database, and hub genes were visualized by Cytoscape. The correlation results were verified with the GSE15824 dataset. Bioinformatic analysis confirmed that ZWINT was significantly positively correlated with kinetochore protein NDC80 homolog (NDC80), serine/threonine-protein kinase PLK1 (PLK1) and spindle and kinetochore associated complex subunit 1 (SKA1) and together are involved in regulating mitosis and the cell cycle of GBM. ZWINT expression was knocked down in U251 and U87 MG GBM cells by lentiviral vectors carrying a small hairpin RNA (shRNA) targeting ZWINT. The effect of ZWINT silencing on cell proliferation, invasion and apoptosis was determined by the Celigo assay, MTT assay, Transwell assay, flow cytometry and caspase-3/7 assay in vitro. A subcutaneous xenograft tumor model was established to explore the influence of ZWINT knockdown on GBM growth in vivo. Our preliminary study demonstrated that ZWINT knockdown effectively inhibited proliferation and invasion and induced apoptosis of GBM cells and notably suppressed GBM growth in vivo. Therefore, we speculate that ZWINT may be a potential therapeutic biomarker for GBM, with NDC80 and PLK1 conjointly involved in regulating cell division and the mitotic cell cycle.

Identification and characterization of N6‐methyladenosine modification of circRNAs in glioblastoma

“…36 In addition, ZWINT is significantly positively correlated with the mitochondrial protein NDC80, the serine/threonine protein kinase PLK1 (PLK1), and complex spindle and mitochondrial-related subunit 1 (SKA1) and is associated with the regulation of mitosis and the cell cycle in GBM. 37 In primary glioblastoma, the low tumour copy number of the F13A1 gene fragment is associated with poor survival, 38 which is inconsistent with our sequencing results; this complex mechanism needs further study. These key molecules can be used as the preferred genes for future research on the function and mechanism of N6-methyladenosine-mediated GBM development.…”

“…Of the five circRNAs of interest we selected, BUB1 has been considered a novel therapeutic target for glioblastoma and plays a key role in promoting tumour proliferation and radiation resistance in GBM in a forkhead box protein M1 (FOXM1)–dependent manner 36 . In addition, ZWINT is significantly positively correlated with the mitochondrial protein NDC80, the serine/threonine protein kinase PLK1 (PLK1), and complex spindle and mitochondrial‐related subunit 1 (SKA1) and is associated with the regulation of mitosis and the cell cycle in GBM 37 . In primary glioblastoma, the low tumour copy number of the F13A1 gene fragment is associated with poor survival, 38 which is inconsistent with our sequencing results; this complex mechanism needs further study.…”

To Ubiquitinate or Not to Ubiquitinate: TRIM17 in Cell Life and Death

“…TRIM17 is also involved in mitosis by inducing the degradation of key components of the mitotic spindle machinery, midbodies and the kinetochore protein ZWINT, via autophagy and UPS, respectively [ 68 , 73 ]. Notably, ZWINT is upregulated in many human cancers and is associated with poor clinical prognosis and early recurrence [ 145 , 146 ]. Conversely, ZWINT knockdown effectively inhibits proliferation of glioblastoma cells in vitro and suppresses glioblastoma growth in vivo [ 146 ].…”

“…Notably, ZWINT is upregulated in many human cancers and is associated with poor clinical prognosis and early recurrence [ 145 , 146 ]. Conversely, ZWINT knockdown effectively inhibits proliferation of glioblastoma cells in vitro and suppresses glioblastoma growth in vivo [ 146 ]. Therefore, it would not be surprising that dysregulation of TRIM17 participates in tumorigenesis and chemoresistance by altering apoptosis and mitosis regulation.…”

Bioinformatics identification of hub genes and signaling pathways regulated by intravenous immunoglobulin treatment in acute Kawasaki disease

“…Chromosome instability is also affected by ZWINT (27). Therefore, the present study on ZWINT is mostly focused on tumors, including breast cancer (25), hepatocellular carcinoma (28) and glioblastoma (29). Furthermore, upregulation of ZWINT has a positive regulatory effect on the antiviral signaling pathway (28).…”