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The long non-coding RNA TAZ-AS202 promotes lung cancer progression via regulation of the E2F1 transcription factor and activation of Ephrin signaling

Long non-coding RNAs (lncRNAs) are transcripts without coding potential that are pervasively expressed from the genome and have been increasingly reported to play crucial roles in all aspects of cell biology. They have been also heavily implicated in cancer development and progression, with both onc...

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Autores principales: Gobbi, Giulia, Grieco, Alessandra, Torricelli, Federica, Sauta, Elisabetta, Santandrea, Giacomo, Zanetti, Eleonora, Fantini, Valentina, Reggiani, Francesca, Strocchi, Silvia, Paci, Massimiliano, Vohra, Manik, Saladi, Srinivas Vinod, Ambrosetti, Davide Carlo, Ciarrocchi, Alessia, Sancisi, Valentina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10657417/
https://www.ncbi.nlm.nih.gov/pubmed/37980331
http://dx.doi.org/10.1038/s41419-023-06277-y
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author Gobbi, Giulia
Grieco, Alessandra
Torricelli, Federica
Sauta, Elisabetta
Santandrea, Giacomo
Zanetti, Eleonora
Fantini, Valentina
Reggiani, Francesca
Strocchi, Silvia
Paci, Massimiliano
Vohra, Manik
Saladi, Srinivas Vinod
Ambrosetti, Davide Carlo
Ciarrocchi, Alessia
Sancisi, Valentina
author_facet Gobbi, Giulia
Grieco, Alessandra
Torricelli, Federica
Sauta, Elisabetta
Santandrea, Giacomo
Zanetti, Eleonora
Fantini, Valentina
Reggiani, Francesca
Strocchi, Silvia
Paci, Massimiliano
Vohra, Manik
Saladi, Srinivas Vinod
Ambrosetti, Davide Carlo
Ciarrocchi, Alessia
Sancisi, Valentina
author_sort Gobbi, Giulia
collection PubMed
description Long non-coding RNAs (lncRNAs) are transcripts without coding potential that are pervasively expressed from the genome and have been increasingly reported to play crucial roles in all aspects of cell biology. They have been also heavily implicated in cancer development and progression, with both oncogenic and tumor suppressor functions. In this work, we identified and characterized a novel lncRNA, TAZ-AS202, expressed from the TAZ genomic locus and exerting pro-oncogenic functions in non-small cell lung cancer. TAZ-AS202 expression is under the control of YAP/TAZ-containing transcriptional complexes. We demonstrated that TAZ-AS202 is overexpressed in lung cancer tissue, compared with surrounding lung epithelium. In lung cancer cell lines TAZ-AS202 promotes cell migration and cell invasion. TAZ-AS202 regulates the expression of a set of genes belonging to cancer-associated pathways, including WNT and EPH-Ephrin signaling. The molecular mechanism underlying TAZ-AS202 function does not involve change of TAZ expression or activity, but increases the protein level of the transcription factor E2F1, which in turn regulates the expression of a large set of target genes, including the EPHB2 receptor. Notably, the silencing of both E2F1 and EPHB2 recapitulates TAZ-AS202 silencing cellular phenotype, indicating that they are essential mediators of its activity. Overall, this work unveiled a new regulatory mechanism that, by increasing E2F1 protein, modifies the non-small cell lung cancer cells transcriptional program, leading to enhanced aggressiveness features. The TAZ-AS202/E2F1/EPHB2 axis may be the target for new therapeutic strategies.
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spelling pubmed-106574172023-11-18 The long non-coding RNA TAZ-AS202 promotes lung cancer progression via regulation of the E2F1 transcription factor and activation of Ephrin signaling Gobbi, Giulia Grieco, Alessandra Torricelli, Federica Sauta, Elisabetta Santandrea, Giacomo Zanetti, Eleonora Fantini, Valentina Reggiani, Francesca Strocchi, Silvia Paci, Massimiliano Vohra, Manik Saladi, Srinivas Vinod Ambrosetti, Davide Carlo Ciarrocchi, Alessia Sancisi, Valentina Cell Death Dis Article Long non-coding RNAs (lncRNAs) are transcripts without coding potential that are pervasively expressed from the genome and have been increasingly reported to play crucial roles in all aspects of cell biology. They have been also heavily implicated in cancer development and progression, with both oncogenic and tumor suppressor functions. In this work, we identified and characterized a novel lncRNA, TAZ-AS202, expressed from the TAZ genomic locus and exerting pro-oncogenic functions in non-small cell lung cancer. TAZ-AS202 expression is under the control of YAP/TAZ-containing transcriptional complexes. We demonstrated that TAZ-AS202 is overexpressed in lung cancer tissue, compared with surrounding lung epithelium. In lung cancer cell lines TAZ-AS202 promotes cell migration and cell invasion. TAZ-AS202 regulates the expression of a set of genes belonging to cancer-associated pathways, including WNT and EPH-Ephrin signaling. The molecular mechanism underlying TAZ-AS202 function does not involve change of TAZ expression or activity, but increases the protein level of the transcription factor E2F1, which in turn regulates the expression of a large set of target genes, including the EPHB2 receptor. Notably, the silencing of both E2F1 and EPHB2 recapitulates TAZ-AS202 silencing cellular phenotype, indicating that they are essential mediators of its activity. Overall, this work unveiled a new regulatory mechanism that, by increasing E2F1 protein, modifies the non-small cell lung cancer cells transcriptional program, leading to enhanced aggressiveness features. The TAZ-AS202/E2F1/EPHB2 axis may be the target for new therapeutic strategies. Nature Publishing Group UK 2023-11-18 /pmc/articles/PMC10657417/ /pubmed/37980331 http://dx.doi.org/10.1038/s41419-023-06277-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Gobbi, Giulia
Grieco, Alessandra
Torricelli, Federica
Sauta, Elisabetta
Santandrea, Giacomo
Zanetti, Eleonora
Fantini, Valentina
Reggiani, Francesca
Strocchi, Silvia
Paci, Massimiliano
Vohra, Manik
Saladi, Srinivas Vinod
Ambrosetti, Davide Carlo
Ciarrocchi, Alessia
Sancisi, Valentina
The long non-coding RNA TAZ-AS202 promotes lung cancer progression via regulation of the E2F1 transcription factor and activation of Ephrin signaling
title The long non-coding RNA TAZ-AS202 promotes lung cancer progression via regulation of the E2F1 transcription factor and activation of Ephrin signaling
title_full The long non-coding RNA TAZ-AS202 promotes lung cancer progression via regulation of the E2F1 transcription factor and activation of Ephrin signaling
title_fullStr The long non-coding RNA TAZ-AS202 promotes lung cancer progression via regulation of the E2F1 transcription factor and activation of Ephrin signaling
title_full_unstemmed The long non-coding RNA TAZ-AS202 promotes lung cancer progression via regulation of the E2F1 transcription factor and activation of Ephrin signaling
title_short The long non-coding RNA TAZ-AS202 promotes lung cancer progression via regulation of the E2F1 transcription factor and activation of Ephrin signaling
title_sort long non-coding rna taz-as202 promotes lung cancer progression via regulation of the e2f1 transcription factor and activation of ephrin signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10657417/
https://www.ncbi.nlm.nih.gov/pubmed/37980331
http://dx.doi.org/10.1038/s41419-023-06277-y
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