Kruppel-family zinc finger proteins as emerging epigenetic biomarkers in head and neck squamous cell carcinoma
Abstract Background Krüppel-type zinc finger protein genes located on chromosome 19q13 are aberrantly hypermethylated with high frequency in all anatomic sub-sites of head and neck cancers as well as other epithelial tumours resulting in decreased expression. Methods We examined prognostic significa...
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SAGE Publishing
2023-05-01
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| Series: | Journal of Otolaryngology - Head and Neck Surgery |
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| Online Access: | https://doi.org/10.1186/s40463-023-00640-x |
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| author | Patrick Pearson Kendra Smith Nilita Sood Elizabeth Chia Alicia Follett Michael B. Prystowsky Simon Kirby Thomas J. Belbin |
| author_facet | Patrick Pearson Kendra Smith Nilita Sood Elizabeth Chia Alicia Follett Michael B. Prystowsky Simon Kirby Thomas J. Belbin |
| author_sort | Patrick Pearson |
| collection | DOAJ |
| description | Abstract Background Krüppel-type zinc finger protein genes located on chromosome 19q13 are aberrantly hypermethylated with high frequency in all anatomic sub-sites of head and neck cancers as well as other epithelial tumours resulting in decreased expression. Methods We examined prognostic significance of ZNF154 and ZNF132 expression and DNA methylation in independent patient cohort of about 500 head and neck cancer patients in the Cancer Genome Atlas (TCGA). We also overexpressed these genes in HEK-293 cells, as well as the oral cancer cell line UM-SCC-1. Results In 20 patients from the TCGA cohort of HNSCC patients where ZNF154 and ZNF132 DNA methylation and RNA expression could be compared in tumor and adjacent normal tissue, there was increased DNA methylation and decreased expression of both ZNF154 and ZNF132 in primary tumours. Low ZNF154 and low ZNF132 expression were associated with shorter overall survival in both head and neck squamous cell carcinoma (HNSCC) and lung adenocarcinoma (LUAC patients). While expression of these proteins in HEK-293 cells produced full-length protein, only truncated copies could be expressed in head and neck cancer cells (UM-SCC-1). The truncated version of ZNF154 protein increased doubling time and reduced cell migration in UM-SCC-1 cancer cells. Conclusions Both ZNF132 and ZNF154 represent novel clinically significant biomarkers in head and neck cancer with potential tumour suppressive properties. Future studies will address the underlying molecular mechanisms by which ZNF154 expression in HNSCC contributes to the control of cell growth and migration. Graphical abstract |
| format | Article |
| id | doaj-art-26c0ccd341ab44a99e4b52487ca34524 |
| institution | Kabale University |
| issn | 1916-0216 |
| language | English |
| publishDate | 2023-05-01 |
| publisher | SAGE Publishing |
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| series | Journal of Otolaryngology - Head and Neck Surgery |
| spelling | doaj-art-26c0ccd341ab44a99e4b52487ca345242025-02-03T01:08:33ZengSAGE PublishingJournal of Otolaryngology - Head and Neck Surgery1916-02162023-05-0152111510.1186/s40463-023-00640-xKruppel-family zinc finger proteins as emerging epigenetic biomarkers in head and neck squamous cell carcinomaPatrick Pearson0Kendra Smith1Nilita Sood2Elizabeth Chia3Alicia Follett4Michael B. Prystowsky5Simon Kirby6Thomas J. Belbin7Division of Biomedical Sciences, Faculty of Medicine, Memorial University of NewfoundlandDivision of Biomedical Sciences, Faculty of Medicine, Memorial University of NewfoundlandDiscipline of Oncology, Faculty of Medicine, Memorial University of NewfoundlandDivision of Biomedical Sciences, Faculty of Medicine, Memorial University of NewfoundlandDivision of Biomedical Sciences, Faculty of Medicine, Memorial University of NewfoundlandDepartment of Pathology, Albert Einstein College of MedicineDiscipline of Laboratory Medicine, Faculty of Medicine, Memorial University of NewfoundlandDivision of Biomedical Sciences, Faculty of Medicine, Memorial University of NewfoundlandAbstract Background Krüppel-type zinc finger protein genes located on chromosome 19q13 are aberrantly hypermethylated with high frequency in all anatomic sub-sites of head and neck cancers as well as other epithelial tumours resulting in decreased expression. Methods We examined prognostic significance of ZNF154 and ZNF132 expression and DNA methylation in independent patient cohort of about 500 head and neck cancer patients in the Cancer Genome Atlas (TCGA). We also overexpressed these genes in HEK-293 cells, as well as the oral cancer cell line UM-SCC-1. Results In 20 patients from the TCGA cohort of HNSCC patients where ZNF154 and ZNF132 DNA methylation and RNA expression could be compared in tumor and adjacent normal tissue, there was increased DNA methylation and decreased expression of both ZNF154 and ZNF132 in primary tumours. Low ZNF154 and low ZNF132 expression were associated with shorter overall survival in both head and neck squamous cell carcinoma (HNSCC) and lung adenocarcinoma (LUAC patients). While expression of these proteins in HEK-293 cells produced full-length protein, only truncated copies could be expressed in head and neck cancer cells (UM-SCC-1). The truncated version of ZNF154 protein increased doubling time and reduced cell migration in UM-SCC-1 cancer cells. Conclusions Both ZNF132 and ZNF154 represent novel clinically significant biomarkers in head and neck cancer with potential tumour suppressive properties. Future studies will address the underlying molecular mechanisms by which ZNF154 expression in HNSCC contributes to the control of cell growth and migration. Graphical abstracthttps://doi.org/10.1186/s40463-023-00640-xZNFOral cavitySquamousCarcinoma |
| spellingShingle | Patrick Pearson Kendra Smith Nilita Sood Elizabeth Chia Alicia Follett Michael B. Prystowsky Simon Kirby Thomas J. Belbin Kruppel-family zinc finger proteins as emerging epigenetic biomarkers in head and neck squamous cell carcinoma Journal of Otolaryngology - Head and Neck Surgery ZNF Oral cavity Squamous Carcinoma |
| title | Kruppel-family zinc finger proteins as emerging epigenetic biomarkers in head and neck squamous cell carcinoma |
| title_full | Kruppel-family zinc finger proteins as emerging epigenetic biomarkers in head and neck squamous cell carcinoma |
| title_fullStr | Kruppel-family zinc finger proteins as emerging epigenetic biomarkers in head and neck squamous cell carcinoma |
| title_full_unstemmed | Kruppel-family zinc finger proteins as emerging epigenetic biomarkers in head and neck squamous cell carcinoma |
| title_short | Kruppel-family zinc finger proteins as emerging epigenetic biomarkers in head and neck squamous cell carcinoma |
| title_sort | kruppel family zinc finger proteins as emerging epigenetic biomarkers in head and neck squamous cell carcinoma |
| topic | ZNF Oral cavity Squamous Carcinoma |
| url | https://doi.org/10.1186/s40463-023-00640-x |
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