Effect of NDC80 in human hepatocellular carcinoma

Ju, Linling; Chen, Lin; Li, Junhong; Wang, Yifan; Lu, Rong; Bian, Zhaolian; Shao, Jianghua

doi:10.3748/wjg.v23.i20.3675

Cited by 57 publications

(53 citation statements)

References 30 publications

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“…The mitotic regulator NDC80 is highly expressed in various human malignancies, including hepatocellular carcinoma, colon cancer and osteosarcoma (33)(34)(35). NDC80 is also called Hec1, and its complexes together with NUF2 component of NDC80 kinetochore complex (NUF2), SPC24 component of NDC80 kinetochore complex (SPC24) and SPC25 component of NDC80 kinetochore complex (SPC25) participate in the spindle assembly checkpoint and regulation of mitosis and chromosome segregation (36)(37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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“…It forms a heterotetramer complex with proteins SPC24, SPC25 and NUF2, and the complex has been known to involve in spindle assembly checkpoint signaling, detecting the unaligned chromosomes to assure the correct segregation of chromosomes. Aberrant expression of NDC80 has been reported in several other tumors [38][39][40][41][42] , for instance osteosarcoma, hepatocellulcar carcinoma, colorectal cancer and breast cancer, indicating its potential as a newly bio target.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic Analysis Revealing Mitotic Spindle Assembly regulated NDC80 and MAD2L1 as Prognostic Biomarkers in Non-Small Cell Lung Cancer Development

Wei

Wang

Zhang

et al. 2020

Preprint

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Background Lung cancer has been the leading cause of tumor related death, and 80%~85% of it is non-small cell lung cancer (NSCLC). Even with the rising molecular targeted therapies, for example EGFR, ROS1 and ALK, the treatment is still challenging. The study is to identify credible responsible genes during the development of NSCLC using bioinformatic analysis, developing new prognostic biomarkers and potential gene targets to the disease. Methods Firstly, three genes expression profiles GSE44077, GSE18842 and GSE33532 were picked from Gene Expression Omnibus (GEO) to analyze the genes with different expression level (GDEs) between NSCLC and normal lung samples, and the cellular location, molecular function and the biology pathways the GDEs enriched in were analyzed. Then, gene function modules of GDEs were explored based on the protein-protein interaction network (PPI), and the top module which contains most genes was identified, followed by containing genes annotation and survival analysis. Moreover, multivariate cox regression analysis was performed in addition to the Kaplan meier survival to narrow down the key genes scale. Further, the clinical pathological features of the picked key genes were explored using TCGA data. Results Three GEO profiles shared a total of 664 GDEs, including 232 up-regulated and 432 down-regulated genes. Based on the GDEs PPI network, the top function module containing a total of 69 genes was identified, and 31 of 69 genes were mitotic cell cycle regulation related. And survival analysis of the 31 genes revealed that 17/31 genes statistical significantly related to NSCLC overall survival, including 4 spindle assembly checkpoints, namely NDC80, BUB1B, MAD2L1 and AURKA. Further, multivariate cox regression analysis identified NDC80 and MAD2L1 as independent prognostic indicators in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) respectively. Interestingly, pearson correlation analysis indicated strong connection between the four genes NDC80, BUB1B, MAD2L1 and AURKA, and their clinical pathological features were addressed. Conclusions Using bioinformatic analysis of GEO combined with TCGA data, we revealed two independent prognostic indicators in LUAD and LUSC respectively and analyzed their clinical features. However, more detailed experiments and clinical trials are needed to verify their drug targets role in clinical medical use.

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“…HCC is a leading cause of cancer-associated mortality worldwide, and tumor recurrence and metastasis are major factors that contribute to the poor prognosis of HCC patients (29,30). Previous studies have confirmed that protein ubiquitination serves multiple roles in different biological processes.…”

Section: Discussionmentioning

confidence: 99%

High expression of ubiquitin-conjugating enzyme E2A predicts poor prognosis in hepatocellular carcinoma

Shen

et al. 2018

Oncol Lett

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Abstract. The present study aimed to illustrate the association of the expression of ubiquitin-conjugating enzyme E2A (UBE2A) with the clinicopathological parameters and prognosis in hepatocellular carcinoma (HCC). The expression levels of UBE2A mRNA and protein in a total of 276 HCC tissues and six liver cell lines was detected by fluorescent quantitative polymerase chain reaction, western blotting and immunohistochemistry. Statistical analysis was also performed to assess the association of the expression of UBE2A with the clinicopathological parameters and prognosis by the GraphPad Prism and SPSS version 21.0 software. UBE2A mRNA and protein were highly expressed in HCC tissues compared with those in the adjacent normal tissue. Immunohistochemical analysis revealed that UBE2A protein was more strongly stained in the 276 paraffin-embedded HCC tissues as compared with the 63 adjacent normal tissue. Statistical analysis also demonstrated that UBE2A expression was significantly associated with histological differentiation, TNM stage and vascular invasion of HCC (P<0.05). Notably, HCC patients with a high expression of UBE2A had a shorter survival time as compared with those with a low expression of UBE2A. There results suggested that UBE2A may be involved in the pathogenesis of HCC and may serve as an important prognostic marker.Further exploration of the involvement of UBE2A in HCC development may provide novel therapeutic targets. IntroductionHepatocellular carcinoma (HCC) is the third leading cause of cancer-associated mortality worldwide and the fifth most common cancer type (1). HCC is a global health burden and its prevalence varies worldwide (2). The incidence rate is reported to be higher in Asia (>20 cases/100,000 individuals) in comparison with that in North America and Europe (<5 cases/100,000 individuals) (3). The prognosis of HCC is poor, as evident by the fact that the number of annual mortality cases (~600,000) is almost equal to the number of new cases diagnosed annually (4). The median rate for 1-year survival is 80% (range, 63-97%), for 3-year survival is 70% (range, 34-78%) and for 5-year survival is 50% (range, 17-69%) (5). Surgery remains the most important treatment strategy for patients with HCC. The 5-year survival rate of patients with early HCC subsequent to resection treatment reaches 50%, although these patients exhibit a high recurrence rate (6,7). Despite advances in the diagnosis (8) and treatment (9) of HCC, the prognosis of this disease remains poor (10). Therefore, further clarification of the mechanisms underlying its development is important (11,12).At present, the prognosis of HCC is predicted based on imaging findings and biomarkers. Various biomarkers, including α-fetoprotein (AFP) (13), des-γ-ca rboxy prothrombin (14) and α-l-fucosidase (15), have been identified over the past three decades. However, accurate indicators for the prognosis of HCC are limited. Consequently, there is an urgency to develop a novel biomarker for the prognosis of HCC.The ubiquitin system serves a ...

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Effect of NDC80 in human hepatocellular carcinoma

Cited by 57 publications

References 30 publications

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

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

Bioinformatic Analysis Revealing Mitotic Spindle Assembly regulated NDC80 and MAD2L1 as Prognostic Biomarkers in Non-Small Cell Lung Cancer Development

High expression of ubiquitin-conjugating enzyme E2A predicts poor prognosis in hepatocellular carcinoma

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