Epigenetic Deregulation of Protein Tyrosine Kinase 6 Promotes Carcinogenesis of Oral Squamous Cell Carcinoma
Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral cancers and causes considerable morbidity and mortality. Epigenetic deregulation is a common mechanism underlying carcinogenesis. DNA methylation deregulation is the epigenetic change observed during the transformation of normal cells...
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MDPI AG
2022-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/9/4495 |
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| author | Yi-Ping Hsieh Ken-Chung Chen Meng-Yen Chen Ling-Yu Huang An-Yu Su Wei-Fan Chiang Wen-Tsung Huang Tze-Ta Huang |
| author_facet | Yi-Ping Hsieh Ken-Chung Chen Meng-Yen Chen Ling-Yu Huang An-Yu Su Wei-Fan Chiang Wen-Tsung Huang Tze-Ta Huang |
| author_sort | Yi-Ping Hsieh |
| collection | DOAJ |
| description | Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral cancers and causes considerable morbidity and mortality. Epigenetic deregulation is a common mechanism underlying carcinogenesis. DNA methylation deregulation is the epigenetic change observed during the transformation of normal cells to precancerous and eventually cancer cells. This study investigated the DNA methylation patterns of <i>PTK6</i> during the development of OSCC. Bisulfite genomic DNA sequencing was performed to determine the <i>PTK6</i> methylation level. OSCC animal models were established to examine changes in PTK6 expression in the different stages of OSCC development. The DNA methylation of <i>PTK6</i> was decreased during the development of OSCC. The mRNA and protein expression of PTK6 was increased in OSCC cell lines compared with human normal oral keratinocytes. In mice, the methylation level of <i>PTK6</i> decreased after treatment with 4-nitroquinoline 1-oxide and arecoline, and the mRNA and protein expression of PTK6 was increased. <i>PTK6</i> hypomethylation can be a diagnostic marker of OSCC. Upregulation of PTK6 promoted the proliferation, migration, and invasion of OSCC cells. PTK6 promoted carcinogenesis and metastasis by increasing STAT3 phosphorylation and ZEB1 expression. The epigenetic deregulation of <i>PTK6</i> can serve as a biomarker for the early detection of OSCC and as a treatment target. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:08:23Z |
| publishDate | 2022-04-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-98a6615651a7400cbc88dad2108d5b7a2023-11-23T08:18:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01239449510.3390/ijms23094495Epigenetic Deregulation of Protein Tyrosine Kinase 6 Promotes Carcinogenesis of Oral Squamous Cell CarcinomaYi-Ping Hsieh0Ken-Chung Chen1Meng-Yen Chen2Ling-Yu Huang3An-Yu Su4Wei-Fan Chiang5Wen-Tsung Huang6Tze-Ta Huang7Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701401, TaiwanInstitute of Oral Medicine, Department of Dentistry, College of Medicine, National Cheng Kung University, Tainan 701401, TaiwanInstitute of Oral Medicine, Department of Dentistry, College of Medicine, National Cheng Kung University, Tainan 701401, TaiwanInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701401, TaiwanDepartment of Dentistry, College of Medicine, National Cheng Kung University, Tainan 701401, TaiwanChi Mei Medical Center, Liouying, Tainan 72263, TaiwanChi Mei Medical Center, Liouying, Tainan 72263, TaiwanInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701401, TaiwanOral squamous cell carcinoma (OSCC) accounts for over 90% of oral cancers and causes considerable morbidity and mortality. Epigenetic deregulation is a common mechanism underlying carcinogenesis. DNA methylation deregulation is the epigenetic change observed during the transformation of normal cells to precancerous and eventually cancer cells. This study investigated the DNA methylation patterns of <i>PTK6</i> during the development of OSCC. Bisulfite genomic DNA sequencing was performed to determine the <i>PTK6</i> methylation level. OSCC animal models were established to examine changes in PTK6 expression in the different stages of OSCC development. The DNA methylation of <i>PTK6</i> was decreased during the development of OSCC. The mRNA and protein expression of PTK6 was increased in OSCC cell lines compared with human normal oral keratinocytes. In mice, the methylation level of <i>PTK6</i> decreased after treatment with 4-nitroquinoline 1-oxide and arecoline, and the mRNA and protein expression of PTK6 was increased. <i>PTK6</i> hypomethylation can be a diagnostic marker of OSCC. Upregulation of PTK6 promoted the proliferation, migration, and invasion of OSCC cells. PTK6 promoted carcinogenesis and metastasis by increasing STAT3 phosphorylation and ZEB1 expression. The epigenetic deregulation of <i>PTK6</i> can serve as a biomarker for the early detection of OSCC and as a treatment target.https://www.mdpi.com/1422-0067/23/9/4495oral squamous cell carcinomaoral squamous cell carcinoma carcinogenesisepigenetic regulationprotein tyrosine kinase 6 (PTK6) |
| spellingShingle | Yi-Ping Hsieh Ken-Chung Chen Meng-Yen Chen Ling-Yu Huang An-Yu Su Wei-Fan Chiang Wen-Tsung Huang Tze-Ta Huang Epigenetic Deregulation of Protein Tyrosine Kinase 6 Promotes Carcinogenesis of Oral Squamous Cell Carcinoma International Journal of Molecular Sciences oral squamous cell carcinoma oral squamous cell carcinoma carcinogenesis epigenetic regulation protein tyrosine kinase 6 (PTK6) |
| title | Epigenetic Deregulation of Protein Tyrosine Kinase 6 Promotes Carcinogenesis of Oral Squamous Cell Carcinoma |
| title_full | Epigenetic Deregulation of Protein Tyrosine Kinase 6 Promotes Carcinogenesis of Oral Squamous Cell Carcinoma |
| title_fullStr | Epigenetic Deregulation of Protein Tyrosine Kinase 6 Promotes Carcinogenesis of Oral Squamous Cell Carcinoma |
| title_full_unstemmed | Epigenetic Deregulation of Protein Tyrosine Kinase 6 Promotes Carcinogenesis of Oral Squamous Cell Carcinoma |
| title_short | Epigenetic Deregulation of Protein Tyrosine Kinase 6 Promotes Carcinogenesis of Oral Squamous Cell Carcinoma |
| title_sort | epigenetic deregulation of protein tyrosine kinase 6 promotes carcinogenesis of oral squamous cell carcinoma |
| topic | oral squamous cell carcinoma oral squamous cell carcinoma carcinogenesis epigenetic regulation protein tyrosine kinase 6 (PTK6) |
| url | https://www.mdpi.com/1422-0067/23/9/4495 |
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