NDC80キネトコア複合体成分は腺様嚢胞癌の潜在的な分子標的である

Adenoid cystic carcinoma (ACC) is a slow-growing malignant tumour that primarily originates from the major and minor salivary glands. The relationship between the NDC80 kinetochore complex component (NUF2) and ACC remains to be elucidated. The present study obtained gene expression information from the Gene Expression Omnibus database (GSE88804 and GSE153002). Differentially expressed genes were identified by using the 'limma' package in R. A protein-protein interaction network was constructed with the Search Tool for Retrieval of Interacting Genes/Proteins database and key genes were extracted using Cytoscape software. Analysis of differential expression levels of hub genes in tumour and normal tissue was performed using Tumour Immune Estimation Resource (TIMER) and GSE36820 profiles. Gene Ontology enrichment was subsequently analysed based on differences in NUF2 expression in tumour tissues. In addition, single sample Gene Set Enrichment Analysis (ssGSEA) was used for the quantitative analysis of immune cell infiltration in ACC. Western blotting and immunohistochemistry were used to assess NUF2 expression levels in tumour and adjacent non-tumour tissues. Small interfering RNA (siRNA) was used to decrease NUF2 expression in ACC cell lines. The biological functions of NUF2 were analysed using Cell Counting Kit-8 and wound healing assays. A total of 248 differential genes were identified by differential expression analyses, with 113 genes upregulated and 135 downregulated. A total of 7 hub genes, namely, CDK1, budding uninhibited by benzimidazoles 1 mitotic checkpoint serine/threonine kinase B, DNA topoisomerase II α, cyclin B2, NUF2, budding uninhibited by benzimidazoles 1 and centromere protein F, were obtained using the 'cytoHubba' plugin. The TIMER, standardized and GSE36820 databases revealed that the expression levels of NUF2 were higher in ACC tissues compared with normal tissue samples. Western blotting and immunohistochemical staining of ACC tissues provided evidence of NUF2 upregulation in ACC tissue compared with normal tissue. NUF2-related genes were enriched in 'ameboidal-type cell migration', 'collagen-containing extracellular matrix' and 'actin binding'. ssGSEA analysis revealed that the expression level of NUF2 was notably associated with activated CD4⁺ T cells, memory B cell and plasmacytoid dendritic cell. ACC cells transfected with NUF2 siRNA exhibited decreased proliferation and migration compared with the control. In conclusion, NUF2 is upregulated in ACC and is associated with immune cell infiltration. Functional studies demonstrated that NUF2 promotes ACC cell proliferation and migration, suggesting its potential as a therapeutic target for ACC.