GeromiRs Are Downregulated in the Tumor Microenvironment during Colon Cancer Colonization of the Liver in a Murine Metastasis Model
dc.contributor.author | Gerovska, Daniela | |
dc.contributor.author | García Gallastegui, Patricia | |
dc.contributor.author | Crende Arruabarrena, Olatz | |
dc.contributor.author | Márquez Clavijo, Joana | |
dc.contributor.author | Larrinaga Embeita, Gorka | |
dc.contributor.author | Unzurrunzaga, Maite | |
dc.contributor.author | Araúzo Bravo, Marcos J. | |
dc.contributor.author | Badiola Echaburu, Iker | |
dc.date.accessioned | 2021-05-17T10:56:37Z | |
dc.date.available | 2021-05-17T10:56:37Z | |
dc.date.issued | 2021-05-01 | |
dc.identifier.citation | International Journal of Molecular Sciences 22(9) : (2021) // Article ID 4819 | es_ES |
dc.identifier.issn | 1422-0067 | |
dc.identifier.uri | http://hdl.handle.net/10810/51414 | |
dc.description.abstract | 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 miR-15a, miR-16, miR-26a, miR-29a, miR-29b and miR-29c. 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 Cercam and Spsb4, identified as prognostic markers in a few cancer types, are associated with downregulated geromiRs and are upregulated in the TME cells. | es_ES |
dc.description.sponsorship | This work was supported by grants from Instituto de Salud Carlos III (AC17/00012), cofounded by the European Union projects (European Regional Development Fund/European Science Foundation, Investing in your future), (ERA-Net program EracoSysMed, JTC-2 2017) and (H2020-FETOPEN, Circular Vision, Project 899417); Diputación Foral de Gipuzkoa and the Department of Economic Development and Infrastructures of the Basque Government (DFG109/20) and the Department of Economic Development and Infrastructures of the Basque Government (DFG109/Grants Health Department of the Basque Government (Spain), RIS3 call, Exp. No. 2020333039 and 2020333001. 20). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/899417 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | |
dc.subject | colorectal cancer | es_ES |
dc.subject | liver metastasis | es_ES |
dc.subject | miRNA | es_ES |
dc.subject | tumor microenvironment | es_ES |
dc.subject | geromiRs | es_ES |
dc.subject | histone modifications | es_ES |
dc.title | GeromiRs Are Downregulated in the Tumor Microenvironment during Colon Cancer Colonization of the Liver in a Murine Metastasis Model | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.date.updated | 2021-05-13T14:32:35Z | |
dc.rights.holder | 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). | es_ES |
dc.relation.publisherversion | https://www.mdpi.com/1422-0067/22/9/4819/htm | es_ES |
dc.identifier.doi | 10.3390/ijms22094819 | |
dc.departamentoes | Biología celular e histología | |
dc.departamentoes | Enfermería | |
dc.departamentoeu | Zelulen biologia eta histologia | |
dc.departamentoeu | Erizaintza |
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Except where otherwise noted, this item's license is described as 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).