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 two 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 regulation factor of BUB1B, which was verified by Chromatin Immunoprecipitation Sequencing samples. In summary, BUB1B was highly expressed in NPC, and HDAC2 may affect cell cycle by regulating BUB1B to promote cancer progression.
Nasopharyngeal carcinoma (NPC) is a highly metastatic and invasive malignant tumor that originates in the nasopharynx. The DNA‐binding protein WD repeat and HMG‐box DNA‐binding protein 1 (WDHD1) are highly expressed in a variety of tumours, but its expression and mechanism of action in NPC have not been reported to date. To investigate the involvement of WDHD1 in NPC, we first mined databases for the gene expression profile of NPC. Immunohistochemistry (IHC) was performed on 338 cases of NPC and 112 non‐NPC samples to verify the results. We report that the expression of WDHD1 is significantly elevated in NPC. ChIP‐seq was used to show that integrin alpha V (ITGAV) and WDHD1 exhibit a significant binding peak in the promoter region of the ITGAV gene. The expression levels of ITGAV and WDHD1 exhibit a significant positive correlation, and IHC was performed to show that ITGAV is highly expressed in NPC. Expression of ITGAV increased after overexpression of WDHD1, suggesting that ITGAV may be a potential target gene of WDHD1. Pathway analysis showed that both genes were closely related to the cell cycle, and flow cytometry was used to further confirm that decreased expression of WDHD1 significantly increased the number of apoptotic cells. In conclusion, our results suggest that expression of WDHD1 is increased in NPC and is likely to be associated with the NPC cell cycle; thus, we propose that WDHD1 may have the potential as a target gene for primary screening and treatment of NPC.
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