Cell Cycle Regulation by Alternative Polyadenylation of CCND1

Global shortening of 3′UTRs by alternative polyadenylation (APA) has been observed in cancer cells. However, the role of APA in cancer remains unknown. CCND1 is a proto-oncogene that regulates progression through the G1-S phase of the cell cycle; moreover, it has been observed to be switching to pro...

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Autores principales: Wang, Qiong, He, Guopei, Hou, Mengmeng, Chen, Liutao, Chen, Shangwu, Xu, Anlong, Fu, Yonggui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931507/
https://www.ncbi.nlm.nih.gov/pubmed/29717174
http://dx.doi.org/10.1038/s41598-018-25141-0
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author Wang, Qiong
He, Guopei
Hou, Mengmeng
Chen, Liutao
Chen, Shangwu
Xu, Anlong
Fu, Yonggui
author_facet Wang, Qiong
He, Guopei
Hou, Mengmeng
Chen, Liutao
Chen, Shangwu
Xu, Anlong
Fu, Yonggui
author_sort Wang, Qiong
collection PubMed
description Global shortening of 3′UTRs by alternative polyadenylation (APA) has been observed in cancer cells. However, the role of APA in cancer remains unknown. CCND1 is a proto-oncogene that regulates progression through the G1-S phase of the cell cycle; moreover, it has been observed to be switching to proximal APA sites in cancer cells. To investigate the biological function of the APA of CCND1, we edited the weak poly(A) signal (PAS) of the proximal APA site to a canonical PAS using the CRISPR/Cas9 method, which can force the cells to use a proximal APA site. Cell cycle profiling and proliferation assays revealed that the proximal APA sites of CCND1 accelerated the cell cycle and promoted cell proliferation, but UTR-APA and CR-APA act via different molecular mechanisms. These results indicate that PAS editing with CRISPR/Cas9 provides a good method by which to study the biological function of APA.
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spelling pubmed-59315072018-08-29 Cell Cycle Regulation by Alternative Polyadenylation of CCND1 Wang, Qiong He, Guopei Hou, Mengmeng Chen, Liutao Chen, Shangwu Xu, Anlong Fu, Yonggui Sci Rep Article Global shortening of 3′UTRs by alternative polyadenylation (APA) has been observed in cancer cells. However, the role of APA in cancer remains unknown. CCND1 is a proto-oncogene that regulates progression through the G1-S phase of the cell cycle; moreover, it has been observed to be switching to proximal APA sites in cancer cells. To investigate the biological function of the APA of CCND1, we edited the weak poly(A) signal (PAS) of the proximal APA site to a canonical PAS using the CRISPR/Cas9 method, which can force the cells to use a proximal APA site. Cell cycle profiling and proliferation assays revealed that the proximal APA sites of CCND1 accelerated the cell cycle and promoted cell proliferation, but UTR-APA and CR-APA act via different molecular mechanisms. These results indicate that PAS editing with CRISPR/Cas9 provides a good method by which to study the biological function of APA. Nature Publishing Group UK 2018-05-01 /pmc/articles/PMC5931507/ /pubmed/29717174 http://dx.doi.org/10.1038/s41598-018-25141-0 Text en © The Author(s) 2018 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
Wang, Qiong
He, Guopei
Hou, Mengmeng
Chen, Liutao
Chen, Shangwu
Xu, Anlong
Fu, Yonggui
Cell Cycle Regulation by Alternative Polyadenylation of CCND1
title Cell Cycle Regulation by Alternative Polyadenylation of CCND1
title_full Cell Cycle Regulation by Alternative Polyadenylation of CCND1
title_fullStr Cell Cycle Regulation by Alternative Polyadenylation of CCND1
title_full_unstemmed Cell Cycle Regulation by Alternative Polyadenylation of CCND1
title_short Cell Cycle Regulation by Alternative Polyadenylation of CCND1
title_sort cell cycle regulation by alternative polyadenylation of ccnd1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931507/
https://www.ncbi.nlm.nih.gov/pubmed/29717174
http://dx.doi.org/10.1038/s41598-018-25141-0
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