Transcriptomic profiling disclosed the role of DNA methylation and histone modifications in tumor-infiltrating myeloid-derived suppressor cell subsets in colorectal cancer
<h3>Background</h3><p dir="ltr">Increased numbers of myeloid-derived suppressor cells (MDSCs) are positively correlated with poor prognosis and reduced survivals of cancer patients. They play central roles in tumor immune evasion and tumor metastasis. However, limited dat...
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2020
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| _version_ | 1864513512254996480 |
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| author | Varun Sasidharan Nair (5396393) |
| author2 | Reem Saleh (3513056) Salman M. Toor (8854751) Rowaida Z. Taha (8854754) Ayman A. Ahmed (18513762) Mohamed A. Kurer (18513765) Khaled Murshed (8309781) Nehad M. Alajez (7397276) Mohamed Abu Nada (8309784) Eyad Elkord (5396390) |
| author2_role | author author author author author author author author author |
| author_facet | Varun Sasidharan Nair (5396393) Reem Saleh (3513056) Salman M. Toor (8854751) Rowaida Z. Taha (8854754) Ayman A. Ahmed (18513762) Mohamed A. Kurer (18513765) Khaled Murshed (8309781) Nehad M. Alajez (7397276) Mohamed Abu Nada (8309784) Eyad Elkord (5396390) |
| author_role | author |
| dc.creator.none.fl_str_mv | Varun Sasidharan Nair (5396393) Reem Saleh (3513056) Salman M. Toor (8854751) Rowaida Z. Taha (8854754) Ayman A. Ahmed (18513762) Mohamed A. Kurer (18513765) Khaled Murshed (8309781) Nehad M. Alajez (7397276) Mohamed Abu Nada (8309784) Eyad Elkord (5396390) |
| dc.date.none.fl_str_mv | 2020-01-15T06:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1186/s13148-020-0808-9 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Transcriptomic_profiling_disclosed_the_role_of_DNA_methylation_and_histone_modifications_in_tumor-infiltrating_myeloid-derived_suppressor_cell_subsets_in_colorectal_cancer/26114428 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Genetics Biomedical and clinical sciences Immunology Oncology and carcinogenesis Myeloid-derived suppressor cells Colorectal cancer Transcriptomic profile DNA methylation Histone modifications |
| dc.title.none.fl_str_mv | Transcriptomic profiling disclosed the role of DNA methylation and histone modifications in tumor-infiltrating myeloid-derived suppressor cell subsets in colorectal cancer |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <h3>Background</h3><p dir="ltr">Increased numbers of myeloid-derived suppressor cells (MDSCs) are positively correlated with poor prognosis and reduced survivals of cancer patients. They play central roles in tumor immune evasion and tumor metastasis. However, limited data are available on phenotypic/transcriptomic characteristics of the different MDSCs subsets in cancer. These cells include immature (I-MDSCs), monocytic (M-MDSCs), and polymorphonuclear/granulocytic (PMN-MDSCs).</p><h3>Methods</h3><p dir="ltr">Phenotypic characterization of myeloid subsets from 27 colorectal cancer (CRC) patients was assessed by flow cytometric analyses. RNA-sequencing of sorted I-MDSCs, PMN-MDSCs, and antigen-presenting cells (APCs) was also performed.</p><h3>Results</h3><p dir="ltr">We found that the levels of I-MDSCs and PMN-MDSCs were increased in tumor tissues (TT), compared with normal tissues (NT) in colorectal cancer. Our functional annotation analyses showed that genes associated with histone deacetylase (HDAC) activation- and DNA methylation-mediated transcriptional silencing were upregulated, and histone acetyl transferase (HAT)-related genes were downregulated in tumor-infiltrating I-MDSCs. Moreover, pathways implicated in cell trafficking and immune suppression, including Wnt, interleukin-6 (IL-6), and mitogen-activated protein kinase (MAPK) signaling, were upregulated in I-MDSCs. Notably, PMN-MDSCs showed downregulation in genes related to DNA methylation and HDAC binding. Using an ex vivo model, we found that inhibition of HDAC activation or neutralization of IL-6 in CRC tumor tissues downregulates the expression of genes associated with immunosuppression and myeloid cell chemotaxis, confirming the importance of HDAC activation and IL-6 signaling pathway in MDSC function and chemotaxis.</p><h3>Conclusions</h3><p dir="ltr">This study provides novel insights into the epigenetic regulations and other molecular pathways in different myeloid cell subsets within the CRC tumor microenvironment (TME), giving opportunities to potential targets for therapeutic benefits.</p><h2>Other Information</h2><p dir="ltr">Published in: Clinical Epigenetics<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s13148-020-0808-9" target="_blank">https://dx.doi.org/10.1186/s13148-020-0808-9</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_87fde20b158ef764fa97c10dde7bec0a |
| identifier_str_mv | 10.1186/s13148-020-0808-9 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26114428 |
| publishDate | 2020 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Transcriptomic profiling disclosed the role of DNA methylation and histone modifications in tumor-infiltrating myeloid-derived suppressor cell subsets in colorectal cancerVarun Sasidharan Nair (5396393)Reem Saleh (3513056)Salman M. Toor (8854751)Rowaida Z. Taha (8854754)Ayman A. Ahmed (18513762)Mohamed A. Kurer (18513765)Khaled Murshed (8309781)Nehad M. Alajez (7397276)Mohamed Abu Nada (8309784)Eyad Elkord (5396390)Biological sciencesBiochemistry and cell biologyGeneticsBiomedical and clinical sciencesImmunologyOncology and carcinogenesisMyeloid-derived suppressor cellsColorectal cancerTranscriptomic profileDNA methylationHistone modifications<h3>Background</h3><p dir="ltr">Increased numbers of myeloid-derived suppressor cells (MDSCs) are positively correlated with poor prognosis and reduced survivals of cancer patients. They play central roles in tumor immune evasion and tumor metastasis. However, limited data are available on phenotypic/transcriptomic characteristics of the different MDSCs subsets in cancer. These cells include immature (I-MDSCs), monocytic (M-MDSCs), and polymorphonuclear/granulocytic (PMN-MDSCs).</p><h3>Methods</h3><p dir="ltr">Phenotypic characterization of myeloid subsets from 27 colorectal cancer (CRC) patients was assessed by flow cytometric analyses. RNA-sequencing of sorted I-MDSCs, PMN-MDSCs, and antigen-presenting cells (APCs) was also performed.</p><h3>Results</h3><p dir="ltr">We found that the levels of I-MDSCs and PMN-MDSCs were increased in tumor tissues (TT), compared with normal tissues (NT) in colorectal cancer. Our functional annotation analyses showed that genes associated with histone deacetylase (HDAC) activation- and DNA methylation-mediated transcriptional silencing were upregulated, and histone acetyl transferase (HAT)-related genes were downregulated in tumor-infiltrating I-MDSCs. Moreover, pathways implicated in cell trafficking and immune suppression, including Wnt, interleukin-6 (IL-6), and mitogen-activated protein kinase (MAPK) signaling, were upregulated in I-MDSCs. Notably, PMN-MDSCs showed downregulation in genes related to DNA methylation and HDAC binding. Using an ex vivo model, we found that inhibition of HDAC activation or neutralization of IL-6 in CRC tumor tissues downregulates the expression of genes associated with immunosuppression and myeloid cell chemotaxis, confirming the importance of HDAC activation and IL-6 signaling pathway in MDSC function and chemotaxis.</p><h3>Conclusions</h3><p dir="ltr">This study provides novel insights into the epigenetic regulations and other molecular pathways in different myeloid cell subsets within the CRC tumor microenvironment (TME), giving opportunities to potential targets for therapeutic benefits.</p><h2>Other Information</h2><p dir="ltr">Published in: Clinical Epigenetics<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s13148-020-0808-9" target="_blank">https://dx.doi.org/10.1186/s13148-020-0808-9</a></p>2020-01-15T06:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1186/s13148-020-0808-9https://figshare.com/articles/journal_contribution/Transcriptomic_profiling_disclosed_the_role_of_DNA_methylation_and_histone_modifications_in_tumor-infiltrating_myeloid-derived_suppressor_cell_subsets_in_colorectal_cancer/26114428CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/261144282020-01-15T06:00:00Z |
| spellingShingle | Transcriptomic profiling disclosed the role of DNA methylation and histone modifications in tumor-infiltrating myeloid-derived suppressor cell subsets in colorectal cancer Varun Sasidharan Nair (5396393) Biological sciences Biochemistry and cell biology Genetics Biomedical and clinical sciences Immunology Oncology and carcinogenesis Myeloid-derived suppressor cells Colorectal cancer Transcriptomic profile DNA methylation Histone modifications |
| status_str | publishedVersion |
| title | Transcriptomic profiling disclosed the role of DNA methylation and histone modifications in tumor-infiltrating myeloid-derived suppressor cell subsets in colorectal cancer |
| title_full | Transcriptomic profiling disclosed the role of DNA methylation and histone modifications in tumor-infiltrating myeloid-derived suppressor cell subsets in colorectal cancer |
| title_fullStr | Transcriptomic profiling disclosed the role of DNA methylation and histone modifications in tumor-infiltrating myeloid-derived suppressor cell subsets in colorectal cancer |
| title_full_unstemmed | Transcriptomic profiling disclosed the role of DNA methylation and histone modifications in tumor-infiltrating myeloid-derived suppressor cell subsets in colorectal cancer |
| title_short | Transcriptomic profiling disclosed the role of DNA methylation and histone modifications in tumor-infiltrating myeloid-derived suppressor cell subsets in colorectal cancer |
| title_sort | Transcriptomic profiling disclosed the role of DNA methylation and histone modifications in tumor-infiltrating myeloid-derived suppressor cell subsets in colorectal cancer |
| topic | Biological sciences Biochemistry and cell biology Genetics Biomedical and clinical sciences Immunology Oncology and carcinogenesis Myeloid-derived suppressor cells Colorectal cancer Transcriptomic profile DNA methylation Histone modifications |