c-Myc-activated USP2-AS1 suppresses senescence and promotes tumor progression via stabilization of E2F1 mRNA

The c-Myc oncoprotein plays a prominent role in cancer initiation, progression, and maintenance. Long noncoding RNAs (lncRNAs) are recently emerging as critical regulators of the c-Myc signaling pathway. Here, we report the lncRNA USP2-AS1 as a direct transcriptional target of c-Myc. Functionally, U...

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Autores principales: Li, Bingyan, Zhang, Guang, Wang, Zhongyu, Yang, Yang, Wang, Chenfeng, Fang, Debao, Liu, Kaiyue, Wang, Fang, Mei, Yide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551278/
https://www.ncbi.nlm.nih.gov/pubmed/34707111
http://dx.doi.org/10.1038/s41419-021-04330-2
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author Li, Bingyan
Zhang, Guang
Wang, Zhongyu
Yang, Yang
Wang, Chenfeng
Fang, Debao
Liu, Kaiyue
Wang, Fang
Mei, Yide
author_facet Li, Bingyan
Zhang, Guang
Wang, Zhongyu
Yang, Yang
Wang, Chenfeng
Fang, Debao
Liu, Kaiyue
Wang, Fang
Mei, Yide
author_sort Li, Bingyan
collection PubMed
description The c-Myc oncoprotein plays a prominent role in cancer initiation, progression, and maintenance. Long noncoding RNAs (lncRNAs) are recently emerging as critical regulators of the c-Myc signaling pathway. Here, we report the lncRNA USP2-AS1 as a direct transcriptional target of c-Myc. Functionally, USP2-AS1 inhibits cellular senescence and acts as an oncogenic molecule by inducing E2F1 expression. Mechanistically, USP2-AS1 associates with the RNA-binding protein G3BP1 and facilitates the interaction of G3BP1 to E2F1 3′-untranslated region, thereby leading to the stabilization of E2F1 messenger RNA. Furthermore, USP2-AS1 is shown as a mediator of the oncogenic function of c-Myc via the regulation of E2F1. Together, these findings suggest that USP2-AS1 is a negative regulator of cellular senescence and also implicates USP2-AS1 as an important player in mediating c-Myc function.
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spelling pubmed-85512782021-10-29 c-Myc-activated USP2-AS1 suppresses senescence and promotes tumor progression via stabilization of E2F1 mRNA Li, Bingyan Zhang, Guang Wang, Zhongyu Yang, Yang Wang, Chenfeng Fang, Debao Liu, Kaiyue Wang, Fang Mei, Yide Cell Death Dis Article The c-Myc oncoprotein plays a prominent role in cancer initiation, progression, and maintenance. Long noncoding RNAs (lncRNAs) are recently emerging as critical regulators of the c-Myc signaling pathway. Here, we report the lncRNA USP2-AS1 as a direct transcriptional target of c-Myc. Functionally, USP2-AS1 inhibits cellular senescence and acts as an oncogenic molecule by inducing E2F1 expression. Mechanistically, USP2-AS1 associates with the RNA-binding protein G3BP1 and facilitates the interaction of G3BP1 to E2F1 3′-untranslated region, thereby leading to the stabilization of E2F1 messenger RNA. Furthermore, USP2-AS1 is shown as a mediator of the oncogenic function of c-Myc via the regulation of E2F1. Together, these findings suggest that USP2-AS1 is a negative regulator of cellular senescence and also implicates USP2-AS1 as an important player in mediating c-Myc function. Nature Publishing Group UK 2021-10-27 /pmc/articles/PMC8551278/ /pubmed/34707111 http://dx.doi.org/10.1038/s41419-021-04330-2 Text en © The Author(s) 2021 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
Li, Bingyan
Zhang, Guang
Wang, Zhongyu
Yang, Yang
Wang, Chenfeng
Fang, Debao
Liu, Kaiyue
Wang, Fang
Mei, Yide
c-Myc-activated USP2-AS1 suppresses senescence and promotes tumor progression via stabilization of E2F1 mRNA
title c-Myc-activated USP2-AS1 suppresses senescence and promotes tumor progression via stabilization of E2F1 mRNA
title_full c-Myc-activated USP2-AS1 suppresses senescence and promotes tumor progression via stabilization of E2F1 mRNA
title_fullStr c-Myc-activated USP2-AS1 suppresses senescence and promotes tumor progression via stabilization of E2F1 mRNA
title_full_unstemmed c-Myc-activated USP2-AS1 suppresses senescence and promotes tumor progression via stabilization of E2F1 mRNA
title_short c-Myc-activated USP2-AS1 suppresses senescence and promotes tumor progression via stabilization of E2F1 mRNA
title_sort c-myc-activated usp2-as1 suppresses senescence and promotes tumor progression via stabilization of e2f1 mrna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551278/
https://www.ncbi.nlm.nih.gov/pubmed/34707111
http://dx.doi.org/10.1038/s41419-021-04330-2
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