GeromiRs Are Downregulated in the Tumor Microenvironment during Colon Cancer Colonization of the Liver in a Murine Metastasis Model
Cancer is a phenomenon broadly related to ageing in various ways such as cell cycle deregulation, metabolic defects or telomerases dysfunction as principal processes. Although the tumor cell is the main actor in cancer progression, it is not the only element of the disease. Cells and the matrix surr...
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MDPI AG
2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/9/4819 |
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| author | Daniela Gerovska Patricia Garcia-Gallastegi Olatz Crende Joana Márquez Gorka Larrinaga Maite Unzurrunzaga Marcos J. Araúzo-Bravo Iker Badiola |
| author_facet | Daniela Gerovska Patricia Garcia-Gallastegi Olatz Crende Joana Márquez Gorka Larrinaga Maite Unzurrunzaga Marcos J. Araúzo-Bravo Iker Badiola |
| author_sort | Daniela Gerovska |
| collection | DOAJ |
| description | Cancer is a phenomenon broadly related to ageing in various ways such as cell cycle deregulation, metabolic defects or telomerases dysfunction as principal processes. Although the tumor cell is the main actor in cancer progression, it is not the only element of the disease. Cells and the matrix surrounding the tumor, called the tumor microenvironment (TME), play key roles in cancer progression. Phenotypic changes of the TME are indispensable for disease progression and a few of these transformations are produced by epigenetic changes including miRNA dysregulation. In this study, we found that a specific group of miRNAs in the liver TME produced by colon cancer called geromiRs, which are miRNAs related to the ageing process, are significantly downregulated. The three principal cell types involved in the liver TME, namely, liver sinusoidal endothelial cells, hepatic stellate (Ito) cells and Kupffer cells, were isolated from a murine hepatic metastasis model, and the miRNA and gene expression profiles were studied. From the 115 geromiRs and their associated hallmarks of aging, which we compiled from the literature, 75 were represented in the used microarrays, 26 out of them were downregulated in the TME cells during colon cancer colonization of the liver, and none of them were upregulated. The histone modification hallmark of the downregulated geromiRs is significantly enriched with the geromiRs <i>miR-15a</i>, <i>miR-16</i>, <i>miR-26a</i>, <i>miR-29a</i>, <i>miR-29b</i> and <i>miR-29c</i>. We built a network of all of the geromiRs downregulated in the TME cells and their gene targets from the MirTarBase database, and we analyzed the expression of these geromiR gene targets in the TME. We found that <i>Cercam</i> and <i>Spsb4</i>, identified as prognostic markers in a few cancer types, are associated with downregulated geromiRs and are upregulated in the TME cells. |
| first_indexed | 2024-03-10T11:45:01Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T11:45:01Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-24ac6c94cd904a559d24e32811eaac492023-11-21T18:08:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-01229481910.3390/ijms22094819GeromiRs Are Downregulated in the Tumor Microenvironment during Colon Cancer Colonization of the Liver in a Murine Metastasis ModelDaniela Gerovska0Patricia Garcia-Gallastegi1Olatz Crende2Joana Márquez3Gorka Larrinaga4Maite Unzurrunzaga5Marcos J. Araúzo-Bravo6Iker Badiola7Computational Biology and Systems Biomedicine Group, Biodonostia Health Research Institute, C/Doctor Beguiristain s/n, 20014 San Sebastián, SpainDepartment of Cell Biology and Histology, Faculty of Medicine and Nursing, University of Basque Country (UPV/EHU), 48940 Leioa, SpainDepartment of Cell Biology and Histology, Faculty of Medicine and Nursing, University of Basque Country (UPV/EHU), 48940 Leioa, SpainDepartment of Cell Biology and Histology, Faculty of Medicine and Nursing, University of Basque Country (UPV/EHU), 48940 Leioa, SpainDepartment of Nursing I, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainCentro Salud Legazpi OSI Goierri-Urola Garaia-Osakidetza, 20230 Legazpia, SpainComputational Biology and Systems Biomedicine Group, Biodonostia Health Research Institute, C/Doctor Beguiristain s/n, 20014 San Sebastián, SpainDepartment of Cell Biology and Histology, Faculty of Medicine and Nursing, University of Basque Country (UPV/EHU), 48940 Leioa, SpainCancer is a phenomenon broadly related to ageing in various ways such as cell cycle deregulation, metabolic defects or telomerases dysfunction as principal processes. Although the tumor cell is the main actor in cancer progression, it is not the only element of the disease. Cells and the matrix surrounding the tumor, called the tumor microenvironment (TME), play key roles in cancer progression. Phenotypic changes of the TME are indispensable for disease progression and a few of these transformations are produced by epigenetic changes including miRNA dysregulation. In this study, we found that a specific group of miRNAs in the liver TME produced by colon cancer called geromiRs, which are miRNAs related to the ageing process, are significantly downregulated. The three principal cell types involved in the liver TME, namely, liver sinusoidal endothelial cells, hepatic stellate (Ito) cells and Kupffer cells, were isolated from a murine hepatic metastasis model, and the miRNA and gene expression profiles were studied. From the 115 geromiRs and their associated hallmarks of aging, which we compiled from the literature, 75 were represented in the used microarrays, 26 out of them were downregulated in the TME cells during colon cancer colonization of the liver, and none of them were upregulated. The histone modification hallmark of the downregulated geromiRs is significantly enriched with the geromiRs <i>miR-15a</i>, <i>miR-16</i>, <i>miR-26a</i>, <i>miR-29a</i>, <i>miR-29b</i> and <i>miR-29c</i>. We built a network of all of the geromiRs downregulated in the TME cells and their gene targets from the MirTarBase database, and we analyzed the expression of these geromiR gene targets in the TME. We found that <i>Cercam</i> and <i>Spsb4</i>, identified as prognostic markers in a few cancer types, are associated with downregulated geromiRs and are upregulated in the TME cells.https://www.mdpi.com/1422-0067/22/9/4819colorectal cancerliver metastasismiRNAtumor microenvironmentgeromiRshistone modifications |
| spellingShingle | Daniela Gerovska Patricia Garcia-Gallastegi Olatz Crende Joana Márquez Gorka Larrinaga Maite Unzurrunzaga Marcos J. Araúzo-Bravo Iker Badiola GeromiRs Are Downregulated in the Tumor Microenvironment during Colon Cancer Colonization of the Liver in a Murine Metastasis Model International Journal of Molecular Sciences colorectal cancer liver metastasis miRNA tumor microenvironment geromiRs histone modifications |
| title | GeromiRs Are Downregulated in the Tumor Microenvironment during Colon Cancer Colonization of the Liver in a Murine Metastasis Model |
| title_full | GeromiRs Are Downregulated in the Tumor Microenvironment during Colon Cancer Colonization of the Liver in a Murine Metastasis Model |
| title_fullStr | GeromiRs Are Downregulated in the Tumor Microenvironment during Colon Cancer Colonization of the Liver in a Murine Metastasis Model |
| title_full_unstemmed | GeromiRs Are Downregulated in the Tumor Microenvironment during Colon Cancer Colonization of the Liver in a Murine Metastasis Model |
| title_short | GeromiRs Are Downregulated in the Tumor Microenvironment during Colon Cancer Colonization of the Liver in a Murine Metastasis Model |
| title_sort | geromirs are downregulated in the tumor microenvironment during colon cancer colonization of the liver in a murine metastasis model |
| topic | colorectal cancer liver metastasis miRNA tumor microenvironment geromiRs histone modifications |
| url | https://www.mdpi.com/1422-0067/22/9/4819 |
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