Overexpression of Zwint predicts poor prognosis and promotes the proliferation of hepatocellular carcinoma by regulating cell-cycle-related proteins

Abstract

IntroductionZwint, a centromere-complex component required for the mitotic spindle checkpoint, has been reported to be overexpressed in different human cancers, but it has not been studied in human hepatocellular carcinoma (HCC).Materials and methodsThe role of Zwint in hepatocellular carcinoma cell proliferation capacities was evaluated by using cell counting kit-8 (CCK8), flow cytometry, clone formation and tumor formation assay in nude mice. Western blot analysis and qPCR assay were performed to assess Zwint interacting with cell-cycle-related proteins.ResultsWe report that ZWINT mRNA and protein expression were upregulated in HCC samples and cell lines. An independent set of 106 HCC-tissue pairs and corresponding noncancerous tissues was evaluated for Zwint expression using immunohistochemistry, and elevated Zwint expression in HCC tissues was significantly correlated with clinicopathological features, such as tumor size and number. Kaplan–Meier survival and Cox regression analysis revealed that high expression of Zwint was correlated with poor overall survival and a greater tendency for tumor recurrence. Ectopic expression of Zwint promoted HCC-cell proliferation, and Zwint expression affected the expression of several cell-cycle proteins, including PCNA, cyclin B1, Cdc25C and CDK1.ConclusionOur findings suggest that upregulation of Zwint may contribute to the progression of HCC and may be a prognostic biomarker and potential therapeutic target for treating HCC.

ZW10 interacting kinetochore protein may serve as a prognostic biomarker for human breast cancer: An integrated bioinformatics analysis

“…Previous studies have examined the expression and roles of ZWINT in multiple types of cancer (7)(8)(9)11,12). Endo et al (10) demonstrated that the interaction of ZWINT with Terf/TRIM17 resulted in its degradation and the consequent regulation of cell proliferation in BC MCF-7 and 293-T cells.…”

“…The majority of studies have proposed that ZWINT acts as a structural protein, which is part of the inner kinetochore scaffold and recruits zeste white 10, which is also a centromere protein, to the kinetochore (5,6). Upregulation of ZWINT has been observed in numerous types of cancer, including ovarian and hepatocellular cancer, as well as glioblastoma, and is indicative of a worse prognosis (7)(8)(9). ZWINT depletion has been demonstrated to attenuate cell proliferation in 293-T and BC MCF-7 cells via Terf/tripartite motif containing 17 (TRIM17) signaling (10).…”

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

“…It is known that abnormal mitosis is a common feature of most malignancies. Although the exact role of the molecular makeup of the kinetochore and how individual components of the kinetochore interact with each other are unknown, growing evidence shows that ZWINT is often highly expressed in a number of human cancers and is linked with poor clinical prognosis and early recurrence (8)(9)(10). However, its role in human GBM remains unclear.…”

Identification of potential biomarkers in subtypes of epithelial ovarian cancer

“…ZWINT, as a part of kinetochore complex, is a protein interacting with ZW10 that plays essential role in kinetochore-microtubule attachment, spindle assembly check point function and ensures that chromosomes are divided equally between daughter cells (Wang et al, 2004). Recently, overexpression of ZWINT has been reported in human malignancies including prostate, ovarian, lung, and breast cancers, as well as lung cancer and hepatocellular carcinoma (Xu et al, 2016;Ying et al, 2018;Peng et al, 2019).…”