Analyzing the suppressive properties of ZNF132 and ZNF154 in head and neck squamous carcinoma

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a disease of the head and neck derived from the mucosal epithelium. ZNF154 has been previously shown to have tumour suppressive properties in nasopharynx cancer cell lines. Investigation of the TCGA dataset reveals that patients with low expression of ZNF132 and ZNF154 have statistically significant worse overall survival rate when compared to patients with high expression of each gene. ZNF132 and ZNF154 has been shown to be hypermethylated as well as have reduced gene expression in HNSCC. Overexpression of ZNF154 in the oral cavity cancer cell line UM-SCC1 appears to cause the production of a truncated ZNF154 protein. Additionally, this causes the production of a shortened ZNF154 transcript. Overexpression of ZNF154 in the immortalized kidney cell line HEK293 causes a significant downregulation of both p53 and FOX01. Gene sequencing of ZNF154 overexpressing UM-SCC1 shows a segment of the ZNF154 gene is missing in the coding region of ZNF154. siRNA knockdown of KAP1 in keratinocyte cells causes a significant increase in ZNF154 expression. These results appear to indicate a relationship between KAP1 and ZNF154. We expect that KAP1 is having a regulatory effect on ZNF154 in UM-SCC1 cells, binding downstream in the coding region of ZNF154 causing the production of a shortened transcript. The silencing of ZNF154 likely involves two mechanisms, DNA methylation as well as the KAP1-ZNF complex binding in the coding region of ZNF154.