MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment
Rather than targeting tumour cells directly, elements of the tumour microenvironment can be modulated to sensitize tumours to the effects of therapy. Here we report a unique mechanism by which ectopic microRNA-103 can manipulate tumour-associated endothelial cells to enhance tumour cell death. Using...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2017
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| Online Access: | http://hdl.handle.net/1721.1/107950 https://orcid.org/0000-0003-3811-2369 https://orcid.org/0000-0001-5629-4798 |
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| author | Wilson, RaeAnna Espinosa-Diez, Cristina Kanner, Nathan Chatterjee, Namita Ruhl, Rebecca Hipfinger, Christina Advani, Sunil J. Li, Jie Franovic, Aleksandra Weis, Sara M. Coussens, Lisa M. Chen, Clark C. Cheresh, David A. Anand, Sudarshan Khan, Omar Fizal Anderson, Daniel Griffith Kumar, Sushil, Ph. D. Massachusetts Institute of Technology |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Wilson, RaeAnna Espinosa-Diez, Cristina Kanner, Nathan Chatterjee, Namita Ruhl, Rebecca Hipfinger, Christina Advani, Sunil J. Li, Jie Franovic, Aleksandra Weis, Sara M. Coussens, Lisa M. Chen, Clark C. Cheresh, David A. Anand, Sudarshan Khan, Omar Fizal Anderson, Daniel Griffith Kumar, Sushil, Ph. D. Massachusetts Institute of Technology |
| author_sort | Wilson, RaeAnna |
| collection | MIT |
| description | Rather than targeting tumour cells directly, elements of the tumour microenvironment can be modulated to sensitize tumours to the effects of therapy. Here we report a unique mechanism by which ectopic microRNA-103 can manipulate tumour-associated endothelial cells to enhance tumour cell death. Using gain-and-loss of function approaches, we show that miR-103 exacerbates DNA damage and inhibits angiogenesis in vitro and in vivo. Local, systemic or vascular-targeted delivery of miR-103 in tumour-bearing mice decreased angiogenesis and tumour growth. Mechanistically, miR-103 regulation of its target gene TREX1 in endothelial cells governs the secretion of pro-inflammatory cytokines into the tumour microenvironment. Our data suggest that this inflammatory milieu may potentiate tumour cell death by supporting immune activation and inducing tumour expression of Fas and TRAIL receptors. Our findings reveal miR-mediated crosstalk between vasculature and tumour cells that can be exploited to improve the efficacy of chemotherapy and radiation. |
| first_indexed | 2024-09-23T14:28:39Z |
| format | Article |
| id | mit-1721.1/107950 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:28:39Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1079502022-10-01T21:31:19Z MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment Wilson, RaeAnna Espinosa-Diez, Cristina Kanner, Nathan Chatterjee, Namita Ruhl, Rebecca Hipfinger, Christina Advani, Sunil J. Li, Jie Franovic, Aleksandra Weis, Sara M. Coussens, Lisa M. Chen, Clark C. Cheresh, David A. Anand, Sudarshan Khan, Omar Fizal Anderson, Daniel Griffith Kumar, Sushil, Ph. D. Massachusetts Institute of Technology Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Khan, Omar Fizal Anderson, Daniel Griffith Rather than targeting tumour cells directly, elements of the tumour microenvironment can be modulated to sensitize tumours to the effects of therapy. Here we report a unique mechanism by which ectopic microRNA-103 can manipulate tumour-associated endothelial cells to enhance tumour cell death. Using gain-and-loss of function approaches, we show that miR-103 exacerbates DNA damage and inhibits angiogenesis in vitro and in vivo. Local, systemic or vascular-targeted delivery of miR-103 in tumour-bearing mice decreased angiogenesis and tumour growth. Mechanistically, miR-103 regulation of its target gene TREX1 in endothelial cells governs the secretion of pro-inflammatory cytokines into the tumour microenvironment. Our data suggest that this inflammatory milieu may potentiate tumour cell death by supporting immune activation and inducing tumour expression of Fas and TRAIL receptors. Our findings reveal miR-mediated crosstalk between vasculature and tumour cells that can be exploited to improve the efficacy of chemotherapy and radiation. United States. National Institutes of Health (R00HL112962) United States. National Institutes of Health (R01 HL57900) Oregon Health & Science University. Knight Cancer Institute (2015-Dive-Knight-01) 2017-04-07T17:54:53Z 2017-04-07T17:54:53Z 2016-11 2016-06 Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/107950 Wilson, RaeAnna, Cristina Espinosa-Diez, Nathan Kanner, Namita Chatterjee, Rebecca Ruhl, Christina Hipfinger, Sunil J. Advani, et al. “MicroRNA Regulation of Endothelial TREX1 Reprograms the Tumour Microenvironment.” Nature Communications 7 (November 25, 2016): 13597. https://orcid.org/0000-0003-3811-2369 https://orcid.org/0000-0001-5629-4798 en_US http://dx.doi.org/10.1038/ncomms13597 Nature Communications Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature |
| spellingShingle | Wilson, RaeAnna Espinosa-Diez, Cristina Kanner, Nathan Chatterjee, Namita Ruhl, Rebecca Hipfinger, Christina Advani, Sunil J. Li, Jie Franovic, Aleksandra Weis, Sara M. Coussens, Lisa M. Chen, Clark C. Cheresh, David A. Anand, Sudarshan Khan, Omar Fizal Anderson, Daniel Griffith Kumar, Sushil, Ph. D. Massachusetts Institute of Technology MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment |
| title | MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment |
| title_full | MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment |
| title_fullStr | MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment |
| title_full_unstemmed | MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment |
| title_short | MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment |
| title_sort | microrna regulation of endothelial trex1 reprograms the tumour microenvironment |
| url | http://hdl.handle.net/1721.1/107950 https://orcid.org/0000-0003-3811-2369 https://orcid.org/0000-0001-5629-4798 |
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