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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
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.
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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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