Inflammatory Cells Can Alter the Levels of H3K9ac and γH2AX in Dysplastic Cells and Favor Tumor Phenotype
Oral potentially malignant disorders (OPMD) are clinical presentations that carry an increased risk of cancer development. Currently, epithelial dysplasia grade is based on architectural and cytological epithelial changes and is used to predict the malignant transformation of these lesions. However,...
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MDPI AG
2023-04-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/13/4/662 |
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| author | Camila de Oliveira Barbeiro Darcy Fernandes Mariana Paravani Palaçon Rogerio Moraes Castilho Luciana Yamamoto de Almeida Andreia Bufalino |
| author_facet | Camila de Oliveira Barbeiro Darcy Fernandes Mariana Paravani Palaçon Rogerio Moraes Castilho Luciana Yamamoto de Almeida Andreia Bufalino |
| author_sort | Camila de Oliveira Barbeiro |
| collection | DOAJ |
| description | Oral potentially malignant disorders (OPMD) are clinical presentations that carry an increased risk of cancer development. Currently, epithelial dysplasia grade is based on architectural and cytological epithelial changes and is used to predict the malignant transformation of these lesions. However, predicting which OPMD will progress to a malignant tumor is very challenging. Inflammatory infiltrates can favor cancer development, and recent studies suggest that this association with OPMD lesions may be related to the etiology and/or aggressive clinical behavior of these lesions. Epigenetic changes such as histone modifications may mediate chronic inflammation and also favor tumor cells in immune resistance and evasion. This study aimed to evaluate the relationship between histone acetylation (H3K9ac) and DNA damage in the context of dysplastic lesions with prominent chronic inflammation. Immunofluorescence of “low-risk” and “high-risk” OPMD lesions (<i>n</i> = 24) and inflammatory fibrous hyperplasia (<i>n</i> = 10) as the control group was performed to assess histone acetylation levels and DNA damage through the phosphorylation of H2AX (γH2AX). Cell co-culture assays with PBMCs and oral keratinocyte cell lines (NOK-SI, DOK, and SCC-25) were performed to assess proliferation, adhesion, migration, and epithelial–mesenchymal transition (EMT). Oral dysplastic lesions showed a hypoacetylation of H3K9 and low levels of γH2AX compared to control. The contact of dysplastic oral keratinocytes with PBMCs favored EMT and the loss of cell–cell adhesion. On the other hand, p27 levels increased and cyclin E decreased in DOK, indicating cell cycle arrest. We conclude that the presence of chronic inflammation associated to dysplastic lesions is capable of promoting epigenetic alterations, which in turn can favor the process of malignant transformation. |
| first_indexed | 2024-03-11T04:50:40Z |
| format | Article |
| id | doaj.art-0d1e124e07054a9689e4c0ca174d852f |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-11T04:50:40Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-0d1e124e07054a9689e4c0ca174d852f2023-11-17T20:00:21ZengMDPI AGJournal of Personalized Medicine2075-44262023-04-0113466210.3390/jpm13040662Inflammatory Cells Can Alter the Levels of H3K9ac and γH2AX in Dysplastic Cells and Favor Tumor PhenotypeCamila de Oliveira Barbeiro0Darcy Fernandes1Mariana Paravani Palaçon2Rogerio Moraes Castilho3Luciana Yamamoto de Almeida4Andreia Bufalino5Oral Medicine, Department of Diagnosis and Surgery, School of Dentistry, São Paulo State University (Unesp), Araraquara 14801-903, SP, BrazilOral Medicine, Department of Diagnosis and Surgery, School of Dentistry, São Paulo State University (Unesp), Araraquara 14801-903, SP, BrazilOral Medicine, Department of Diagnosis and Surgery, School of Dentistry, São Paulo State University (Unesp), Araraquara 14801-903, SP, BrazilLaboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan, 1011N University Av, Ann Arbor, MI 48109-1078, USAOral Medicine, Department of Diagnosis and Surgery, School of Dentistry, São Paulo State University (Unesp), Araraquara 14801-903, SP, BrazilOral Medicine, Department of Diagnosis and Surgery, School of Dentistry, São Paulo State University (Unesp), Araraquara 14801-903, SP, BrazilOral potentially malignant disorders (OPMD) are clinical presentations that carry an increased risk of cancer development. Currently, epithelial dysplasia grade is based on architectural and cytological epithelial changes and is used to predict the malignant transformation of these lesions. However, predicting which OPMD will progress to a malignant tumor is very challenging. Inflammatory infiltrates can favor cancer development, and recent studies suggest that this association with OPMD lesions may be related to the etiology and/or aggressive clinical behavior of these lesions. Epigenetic changes such as histone modifications may mediate chronic inflammation and also favor tumor cells in immune resistance and evasion. This study aimed to evaluate the relationship between histone acetylation (H3K9ac) and DNA damage in the context of dysplastic lesions with prominent chronic inflammation. Immunofluorescence of “low-risk” and “high-risk” OPMD lesions (<i>n</i> = 24) and inflammatory fibrous hyperplasia (<i>n</i> = 10) as the control group was performed to assess histone acetylation levels and DNA damage through the phosphorylation of H2AX (γH2AX). Cell co-culture assays with PBMCs and oral keratinocyte cell lines (NOK-SI, DOK, and SCC-25) were performed to assess proliferation, adhesion, migration, and epithelial–mesenchymal transition (EMT). Oral dysplastic lesions showed a hypoacetylation of H3K9 and low levels of γH2AX compared to control. The contact of dysplastic oral keratinocytes with PBMCs favored EMT and the loss of cell–cell adhesion. On the other hand, p27 levels increased and cyclin E decreased in DOK, indicating cell cycle arrest. We conclude that the presence of chronic inflammation associated to dysplastic lesions is capable of promoting epigenetic alterations, which in turn can favor the process of malignant transformation.https://www.mdpi.com/2075-4426/13/4/662co-cultureepithelial dysplasiamalignant transformationperipheral blood mononuclear cell |
| spellingShingle | Camila de Oliveira Barbeiro Darcy Fernandes Mariana Paravani Palaçon Rogerio Moraes Castilho Luciana Yamamoto de Almeida Andreia Bufalino Inflammatory Cells Can Alter the Levels of H3K9ac and γH2AX in Dysplastic Cells and Favor Tumor Phenotype Journal of Personalized Medicine co-culture epithelial dysplasia malignant transformation peripheral blood mononuclear cell |
| title | Inflammatory Cells Can Alter the Levels of H3K9ac and γH2AX in Dysplastic Cells and Favor Tumor Phenotype |
| title_full | Inflammatory Cells Can Alter the Levels of H3K9ac and γH2AX in Dysplastic Cells and Favor Tumor Phenotype |
| title_fullStr | Inflammatory Cells Can Alter the Levels of H3K9ac and γH2AX in Dysplastic Cells and Favor Tumor Phenotype |
| title_full_unstemmed | Inflammatory Cells Can Alter the Levels of H3K9ac and γH2AX in Dysplastic Cells and Favor Tumor Phenotype |
| title_short | Inflammatory Cells Can Alter the Levels of H3K9ac and γH2AX in Dysplastic Cells and Favor Tumor Phenotype |
| title_sort | inflammatory cells can alter the levels of h3k9ac and γh2ax in dysplastic cells and favor tumor phenotype |
| topic | co-culture epithelial dysplasia malignant transformation peripheral blood mononuclear cell |
| url | https://www.mdpi.com/2075-4426/13/4/662 |
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