Unidirectional alteration of methylation and hydroxymethylation at the promoters and differential gene expression in oral squamous cell carcinoma
Background: Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer worldwide. Although overall losses of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) have been previously observed, a genome-wide, single-base-resolution, and simultaneous mapping of 5mC and 5hmC in...
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| Format: | Article |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1269084/full |
| _version_ | 1827794649556713472 |
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| author | Weizhi Zhao Weizhi Zhao Lin Zhu Lin Zhu Qian Gong Qian Gong Suzhen Ma Suzhen Ma Haofeng Xiong Tong Su Zhengqing Wan Zhengqing Wan Danling Wang Danling Wang Danling Wang |
| author_facet | Weizhi Zhao Weizhi Zhao Lin Zhu Lin Zhu Qian Gong Qian Gong Suzhen Ma Suzhen Ma Haofeng Xiong Tong Su Zhengqing Wan Zhengqing Wan Danling Wang Danling Wang Danling Wang |
| author_sort | Weizhi Zhao |
| collection | DOAJ |
| description | Background: Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer worldwide. Although overall losses of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) have been previously observed, a genome-wide, single-base-resolution, and simultaneous mapping of 5mC and 5hmC in OSCC is still unaccomplished. Similarly, the mechanism of how 5mC and 5hmC collectively lead to abnormal gene expression in OSCC is largely unexplored. Using parallel whole-genome bisulfite sequencing (WGBS) and whole-genome oxidative bisulfite sequencing (oxWGBS), we characterized 5mC- and 5hmC-profiles at single-nucleotide resolution in paired primary OSCC samples and their normal adjacent tissues (NATs). We also analyzed the effect of 5mC- and 5hmC-modifications on differential gene expression in OSCC using multi-omics analysis.Results: An overall reduction of both 5mC and 5hmC in various genomic regions have been observed in OSCC samples. At promoter regions, a total of 6,921 differentially methylated regions and 1,024 differentially hydroxymethylated regions were identified in OSCC. Interestingly, compared to bidirectional modification with 5mC and 5hmC, unidirectional modification with 5mC and 5hmC at the promoters is associated with bigger change in the gene expression. Additionally, genes bearing unidirectional modification with 5mC and 5hmC at the promoters are enriched in signaling pathways like cell proliferation, cell differentiation, and receptor tyrosine kinase pathway that are essential for the tumorigenesis. Finally, the grouped expression signature of top 20 genes bearing promoter-unidirectional-modification with 5mC and 5hmC tends to correlate with the clinical outcome of certain subtypes of head and neck squamous cell carcinoma.Conclusion: Using parallel WGBS and oxWGBS analyses, we observed an overall reduction of 5mC- and 5hmC-modifications at various genomic regions in OSCC. Unidirectional modification with 5mC and 5hmC at the promoters is associated with enhanced changes in gene expression in OSCC tissues. Furthermore, such differentially expressed genes bearing unidirectional modifications with 5mC and 5hmC at the promoters might have clinical relevance to the outcome of OSCC. |
| first_indexed | 2024-03-11T18:36:55Z |
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| id | doaj.art-69aeaf5fbe43458290b96ec920c6db31 |
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| language | English |
| last_indexed | 2024-03-11T18:36:55Z |
| publishDate | 2023-10-01 |
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| spelling | doaj.art-69aeaf5fbe43458290b96ec920c6db312023-10-12T17:53:01ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-10-011410.3389/fgene.2023.12690841269084Unidirectional alteration of methylation and hydroxymethylation at the promoters and differential gene expression in oral squamous cell carcinomaWeizhi Zhao0Weizhi Zhao1Lin Zhu2Lin Zhu3Qian Gong4Qian Gong5Suzhen Ma6Suzhen Ma7Haofeng Xiong8Tong Su9Zhengqing Wan10Zhengqing Wan11Danling Wang12Danling Wang13Danling Wang14Institute for Future Sciences, University of South China, Changsha, Hunan, ChinaThe Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, ChinaInstitute for Future Sciences, University of South China, Changsha, Hunan, ChinaThe Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, ChinaInstitute for Future Sciences, University of South China, Changsha, Hunan, ChinaThe Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, ChinaInstitute for Future Sciences, University of South China, Changsha, Hunan, ChinaThe Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, ChinaXiangya Hospital, Central South University, Changsha, Hunan, ChinaXiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Medical Genetics, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, ChinaMOE Key Lab of Rare Pediatric Diseases, School of Life Sciences, University of South China, Changsha, Hunan, ChinaInstitute for Future Sciences, University of South China, Changsha, Hunan, ChinaThe Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, ChinaMOE Key Lab of Rare Pediatric Diseases, School of Life Sciences, University of South China, Changsha, Hunan, ChinaBackground: Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer worldwide. Although overall losses of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) have been previously observed, a genome-wide, single-base-resolution, and simultaneous mapping of 5mC and 5hmC in OSCC is still unaccomplished. Similarly, the mechanism of how 5mC and 5hmC collectively lead to abnormal gene expression in OSCC is largely unexplored. Using parallel whole-genome bisulfite sequencing (WGBS) and whole-genome oxidative bisulfite sequencing (oxWGBS), we characterized 5mC- and 5hmC-profiles at single-nucleotide resolution in paired primary OSCC samples and their normal adjacent tissues (NATs). We also analyzed the effect of 5mC- and 5hmC-modifications on differential gene expression in OSCC using multi-omics analysis.Results: An overall reduction of both 5mC and 5hmC in various genomic regions have been observed in OSCC samples. At promoter regions, a total of 6,921 differentially methylated regions and 1,024 differentially hydroxymethylated regions were identified in OSCC. Interestingly, compared to bidirectional modification with 5mC and 5hmC, unidirectional modification with 5mC and 5hmC at the promoters is associated with bigger change in the gene expression. Additionally, genes bearing unidirectional modification with 5mC and 5hmC at the promoters are enriched in signaling pathways like cell proliferation, cell differentiation, and receptor tyrosine kinase pathway that are essential for the tumorigenesis. Finally, the grouped expression signature of top 20 genes bearing promoter-unidirectional-modification with 5mC and 5hmC tends to correlate with the clinical outcome of certain subtypes of head and neck squamous cell carcinoma.Conclusion: Using parallel WGBS and oxWGBS analyses, we observed an overall reduction of 5mC- and 5hmC-modifications at various genomic regions in OSCC. Unidirectional modification with 5mC and 5hmC at the promoters is associated with enhanced changes in gene expression in OSCC tissues. Furthermore, such differentially expressed genes bearing unidirectional modifications with 5mC and 5hmC at the promoters might have clinical relevance to the outcome of OSCC.https://www.frontiersin.org/articles/10.3389/fgene.2023.1269084/fulloral squamous cell carcinomamulti-omics analysismethylationhydroxymethylationwhole genome bisulfite sequencingwhole genome oxidative bisulfite sequencing |
| spellingShingle | Weizhi Zhao Weizhi Zhao Lin Zhu Lin Zhu Qian Gong Qian Gong Suzhen Ma Suzhen Ma Haofeng Xiong Tong Su Zhengqing Wan Zhengqing Wan Danling Wang Danling Wang Danling Wang Unidirectional alteration of methylation and hydroxymethylation at the promoters and differential gene expression in oral squamous cell carcinoma Frontiers in Genetics oral squamous cell carcinoma multi-omics analysis methylation hydroxymethylation whole genome bisulfite sequencing whole genome oxidative bisulfite sequencing |
| title | Unidirectional alteration of methylation and hydroxymethylation at the promoters and differential gene expression in oral squamous cell carcinoma |
| title_full | Unidirectional alteration of methylation and hydroxymethylation at the promoters and differential gene expression in oral squamous cell carcinoma |
| title_fullStr | Unidirectional alteration of methylation and hydroxymethylation at the promoters and differential gene expression in oral squamous cell carcinoma |
| title_full_unstemmed | Unidirectional alteration of methylation and hydroxymethylation at the promoters and differential gene expression in oral squamous cell carcinoma |
| title_short | Unidirectional alteration of methylation and hydroxymethylation at the promoters and differential gene expression in oral squamous cell carcinoma |
| title_sort | unidirectional alteration of methylation and hydroxymethylation at the promoters and differential gene expression in oral squamous cell carcinoma |
| topic | oral squamous cell carcinoma multi-omics analysis methylation hydroxymethylation whole genome bisulfite sequencing whole genome oxidative bisulfite sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1269084/full |
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