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Nasopharyngeal carcinoma (NPC) has insidious onset, late clinical diagnosis and high recurrence rate, which leads to poor quality of patient life. Therefore, it is necessary to further explore the pathogenesis and therapy targets of NPC. BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) was found to be up-regulated in a variety of cancers, but only one previous study showed that BUB1B was overexpressed in NPC and the sample size was small. The clinical role of BUB1B expression and its underlying mechanism in NPC require more in-depth research. Immunohistochemical samples and public RNA-seq data indicated that BUB1B protein and mRNA expression levels were up-regulated in NPC, and summary receiver operating characteristic curve indicated that BUB1B expression level had a strong ability to distinguish NPC tissues from non-NPC tissues. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were performed and revealed that BUB1B and its related genes were mainly involved in cell cycle and DNA replication. Protein- Protein Interaction were built to interpret the BUB1B molecular mechanism. Histone deacetylase 2 (HDAC2) could be the upstream transcription factor of BUB1B, which was verified by Chromatin Immunoprecipitation Sequencing samples. In summary, BUB1B was highly expressed in NPC, and the predicted BUB1B upstream transcription factor HDAC2 may affect cell cycle by regulating BUB1B to promote cancer progression.

Background: Nasopharyngeal carcinoma (NPC) is a common type of cancer mainly caused by EB virus infection in southern China and Southeast Asia. Zinc finger protein of the cerebellum 2 has been reported to be dysregulated in numerous cancers. However, its role in NPC has not yet been completely investigated. Methods: ZIC2 mRNA expression and clinical role of NPC was explored by Gene Expression Omnibus (GEO) databases and tissue microarrays. Immunohistochemical (IHC) staining was used to assessed the protein expression level of ZIC2 in NPC. Moreover, functional enrichment analyses were performed by the overlapping genes of differentially expressed genes in NPC and ZIC2 related co-expressed genes. Cistrome Data Browser (Cistrome DB) and scatter diagrams displayed the possibility of ATAD2 as a target gene of ZIC2. Last, characteristic phenotype was identified by weighted gene co-expression network analysis (WGCNA).Results: The mRNA expression levels of ZIC2 were significantly increased in NPC within genechips and tissue microarrays (SMD = 2.14; 95% CI = 1.85–2.44). Increased ZIC2 correlated with poor prognosis in NPC patients. The IHC results also showed that ZIC2 protein expression in NPC tissues was remarkably higher than in control tissues. Enrichment analysis showed that genes positively related to ZIC2 are mainly enriched in cell division and in the cell cycle. WGCNA analysis discovered that NPC dataset GSE12452 may be positive correlated with N stage and nagetive correlated with grade. Conclusion: ZIC2 upregulation may promote NPC tumorigenesis through cancer cell proliferation and cell cycle regulation. ATAD2 may produce a marked effect as the downstream target of ZIC2.