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Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs
The transcribed ultraconserved regions (T-UCRs) encode long non-coding RNAs implicated in human carcinogenesis. Their mechanisms of action and the factors regulating their expression in cancers are poorly understood. Here we show that high expression of uc.339 correlates with lower survival in 210 n...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703849/ https://www.ncbi.nlm.nih.gov/pubmed/29180617 http://dx.doi.org/10.1038/s41467-017-01562-9 |
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author | Vannini, Ivan Wise, Petra M. Challagundla, Kishore B. Plousiou, Meropi Raffini, Mirco Bandini, Erika Fanini, Francesca Paliaga, Giorgia Crawford, Melissa Ferracin, Manuela Ivan, Cristina Fabris, Linda Davuluri, Ramana V. Guo, Zhiyi Cortez, Maria Angelica Zhang, Xinna Chen, Lu Zhang, Shuxing Fernandez-Cymering, Cecilia Han, Leng Carloni, Silvia Salvi, Samanta Ling, Hui Murtadha, Mariam Neviani, Paolo Gitlitz, Barbara J. Laird-Offringa, Ite A. Nana-Sinkam, Patrick Negrini, Massimo Liang, Han Amadori, Dino Cimmino, Amelia Calin, George A. Fabbri, Muller |
author_facet | Vannini, Ivan Wise, Petra M. Challagundla, Kishore B. Plousiou, Meropi Raffini, Mirco Bandini, Erika Fanini, Francesca Paliaga, Giorgia Crawford, Melissa Ferracin, Manuela Ivan, Cristina Fabris, Linda Davuluri, Ramana V. Guo, Zhiyi Cortez, Maria Angelica Zhang, Xinna Chen, Lu Zhang, Shuxing Fernandez-Cymering, Cecilia Han, Leng Carloni, Silvia Salvi, Samanta Ling, Hui Murtadha, Mariam Neviani, Paolo Gitlitz, Barbara J. Laird-Offringa, Ite A. Nana-Sinkam, Patrick Negrini, Massimo Liang, Han Amadori, Dino Cimmino, Amelia Calin, George A. Fabbri, Muller |
author_sort | Vannini, Ivan |
collection | PubMed |
description | The transcribed ultraconserved regions (T-UCRs) encode long non-coding RNAs implicated in human carcinogenesis. Their mechanisms of action and the factors regulating their expression in cancers are poorly understood. Here we show that high expression of uc.339 correlates with lower survival in 210 non-small cell lung cancer (NSCLC) patients. We provide evidence from cell lines and primary samples that TP53 directly regulates uc.339. We find that transcribed uc.339 is upregulated in archival NSCLC samples, functioning as a decoy RNA for miR-339-3p, -663b-3p, and -95-5p. As a result, Cyclin E2, a direct target of all these microRNAs is upregulated, promoting cancer growth and migration. Finally, we find that modulation of uc.339 affects microRNA expression. However, overexpression or downregulation of these microRNAs causes no significant variations in uc.339 levels, suggesting a type of interaction for uc.339 that we call “entrapping”. Our results support a key role for uc.339 in lung cancer. |
format | Online Article Text |
id | pubmed-5703849 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57038492017-11-30 Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs Vannini, Ivan Wise, Petra M. Challagundla, Kishore B. Plousiou, Meropi Raffini, Mirco Bandini, Erika Fanini, Francesca Paliaga, Giorgia Crawford, Melissa Ferracin, Manuela Ivan, Cristina Fabris, Linda Davuluri, Ramana V. Guo, Zhiyi Cortez, Maria Angelica Zhang, Xinna Chen, Lu Zhang, Shuxing Fernandez-Cymering, Cecilia Han, Leng Carloni, Silvia Salvi, Samanta Ling, Hui Murtadha, Mariam Neviani, Paolo Gitlitz, Barbara J. Laird-Offringa, Ite A. Nana-Sinkam, Patrick Negrini, Massimo Liang, Han Amadori, Dino Cimmino, Amelia Calin, George A. Fabbri, Muller Nat Commun Article The transcribed ultraconserved regions (T-UCRs) encode long non-coding RNAs implicated in human carcinogenesis. Their mechanisms of action and the factors regulating their expression in cancers are poorly understood. Here we show that high expression of uc.339 correlates with lower survival in 210 non-small cell lung cancer (NSCLC) patients. We provide evidence from cell lines and primary samples that TP53 directly regulates uc.339. We find that transcribed uc.339 is upregulated in archival NSCLC samples, functioning as a decoy RNA for miR-339-3p, -663b-3p, and -95-5p. As a result, Cyclin E2, a direct target of all these microRNAs is upregulated, promoting cancer growth and migration. Finally, we find that modulation of uc.339 affects microRNA expression. However, overexpression or downregulation of these microRNAs causes no significant variations in uc.339 levels, suggesting a type of interaction for uc.339 that we call “entrapping”. Our results support a key role for uc.339 in lung cancer. Nature Publishing Group UK 2017-11-27 /pmc/articles/PMC5703849/ /pubmed/29180617 http://dx.doi.org/10.1038/s41467-017-01562-9 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Vannini, Ivan Wise, Petra M. Challagundla, Kishore B. Plousiou, Meropi Raffini, Mirco Bandini, Erika Fanini, Francesca Paliaga, Giorgia Crawford, Melissa Ferracin, Manuela Ivan, Cristina Fabris, Linda Davuluri, Ramana V. Guo, Zhiyi Cortez, Maria Angelica Zhang, Xinna Chen, Lu Zhang, Shuxing Fernandez-Cymering, Cecilia Han, Leng Carloni, Silvia Salvi, Samanta Ling, Hui Murtadha, Mariam Neviani, Paolo Gitlitz, Barbara J. Laird-Offringa, Ite A. Nana-Sinkam, Patrick Negrini, Massimo Liang, Han Amadori, Dino Cimmino, Amelia Calin, George A. Fabbri, Muller Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs |
title | Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs |
title_full | Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs |
title_fullStr | Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs |
title_full_unstemmed | Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs |
title_short | Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs |
title_sort | transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor micrornas |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703849/ https://www.ncbi.nlm.nih.gov/pubmed/29180617 http://dx.doi.org/10.1038/s41467-017-01562-9 |
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