Genetic and Epigenetic Impact of Chronic Inflammation on Colon Mucosa Cells
Chronic inflammation increases cancer risk, and cancer development is characterized by stepwise accumulation of genetic and epigenetic alterations. During chronic inflammation, infectious agents and intrinsic mediators of inflammatory responses can induce genetic and epigenetic changes. This study t...
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| Format: | Article |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.722835/full |
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| author | Jia He Jia He Jimin Han Jia Liu Ronghua Yang Jingru Wang Xusheng Wang Xiaodong Chen |
| author_facet | Jia He Jia He Jimin Han Jia Liu Ronghua Yang Jingru Wang Xusheng Wang Xiaodong Chen |
| author_sort | Jia He |
| collection | DOAJ |
| description | Chronic inflammation increases cancer risk, and cancer development is characterized by stepwise accumulation of genetic and epigenetic alterations. During chronic inflammation, infectious agents and intrinsic mediators of inflammatory responses can induce genetic and epigenetic changes. This study tried to evaluate both the genetic and epigenetic influence of chronic inflammation on colon mucosa cells. Repetitive dextran sulfate sodium (DSS) treatment induced chronic colitis model. Whole-exome sequencing (WES) (200× coverage) was performed to detect somatic variations in colon mucosa cells. With the use of whole-genome bisulfite sequencing (BS) at 34-fold coverage (17-fold per strand), the methylome of both the colitis and control tissue was comparatively analyzed. Bioinformatics assay showed that there was no significant single-nucleotide polymorphism/insertion or deletion (SNP/InDel) mutation accumulation in colitis tissue, while it accumulated in aged mice. Forty-eight genes with SNP/InDel mutation were overlapped in the three colitis tissues, two (Wnt3a and Lama2) of which are in the cancer development-related signaling pathway. Differentially methylated region (DMR) assay showed that many genes in the colitis tissue are enriched in the cancer development-related signaling pathway, such as PI3K–AKT, Ras, Wnt, TGF-beta, and MAPK signaling pathway. Together, these data suggested that even though chronic inflammation did not obviously increase genetic mutation accumulation, it could both genetically and epigenetically alter some genes related to cancer development. |
| first_indexed | 2024-12-16T13:04:57Z |
| format | Article |
| id | doaj.art-d8e540f6654b4c01a46b60e98388abf6 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-16T13:04:57Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-d8e540f6654b4c01a46b60e98388abf62022-12-21T22:30:46ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-10-011210.3389/fgene.2021.722835722835Genetic and Epigenetic Impact of Chronic Inflammation on Colon Mucosa CellsJia He0Jia He1Jimin Han2Jia Liu3Ronghua Yang4Jingru Wang5Xusheng Wang6Xiaodong Chen7Department of Burn Surgery, The First People’s Hospital of Foshan, Foshan, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou, ChinaDepartment of Burn Surgery, The First People’s Hospital of Foshan, Foshan, ChinaDepartment of Burn Surgery, The First People’s Hospital of Foshan, Foshan, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou, ChinaDepartment of Burn Surgery, The First People’s Hospital of Foshan, Foshan, ChinaChronic inflammation increases cancer risk, and cancer development is characterized by stepwise accumulation of genetic and epigenetic alterations. During chronic inflammation, infectious agents and intrinsic mediators of inflammatory responses can induce genetic and epigenetic changes. This study tried to evaluate both the genetic and epigenetic influence of chronic inflammation on colon mucosa cells. Repetitive dextran sulfate sodium (DSS) treatment induced chronic colitis model. Whole-exome sequencing (WES) (200× coverage) was performed to detect somatic variations in colon mucosa cells. With the use of whole-genome bisulfite sequencing (BS) at 34-fold coverage (17-fold per strand), the methylome of both the colitis and control tissue was comparatively analyzed. Bioinformatics assay showed that there was no significant single-nucleotide polymorphism/insertion or deletion (SNP/InDel) mutation accumulation in colitis tissue, while it accumulated in aged mice. Forty-eight genes with SNP/InDel mutation were overlapped in the three colitis tissues, two (Wnt3a and Lama2) of which are in the cancer development-related signaling pathway. Differentially methylated region (DMR) assay showed that many genes in the colitis tissue are enriched in the cancer development-related signaling pathway, such as PI3K–AKT, Ras, Wnt, TGF-beta, and MAPK signaling pathway. Together, these data suggested that even though chronic inflammation did not obviously increase genetic mutation accumulation, it could both genetically and epigenetically alter some genes related to cancer development.https://www.frontiersin.org/articles/10.3389/fgene.2021.722835/fullchronic colitischronic inflammationSNP/indelDNA methylationcanceraging |
| spellingShingle | Jia He Jia He Jimin Han Jia Liu Ronghua Yang Jingru Wang Xusheng Wang Xiaodong Chen Genetic and Epigenetic Impact of Chronic Inflammation on Colon Mucosa Cells Frontiers in Genetics chronic colitis chronic inflammation SNP/indel DNA methylation cancer aging |
| title | Genetic and Epigenetic Impact of Chronic Inflammation on Colon Mucosa Cells |
| title_full | Genetic and Epigenetic Impact of Chronic Inflammation on Colon Mucosa Cells |
| title_fullStr | Genetic and Epigenetic Impact of Chronic Inflammation on Colon Mucosa Cells |
| title_full_unstemmed | Genetic and Epigenetic Impact of Chronic Inflammation on Colon Mucosa Cells |
| title_short | Genetic and Epigenetic Impact of Chronic Inflammation on Colon Mucosa Cells |
| title_sort | genetic and epigenetic impact of chronic inflammation on colon mucosa cells |
| topic | chronic colitis chronic inflammation SNP/indel DNA methylation cancer aging |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.722835/full |
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