Cargando…
PHF5A promotes colorectal cancerprogression by alternative splicing of TEAD2
Dysregulated alternative splicing (AS) plays critical roles in driving cancer progression, and the underlying mechanisms remain largely unknown. Here, we demonstrated that PHF5A, a component of U2 small nuclear ribonucleoproteins, was frequently upregulated in colorectal cancer (CRC) samples and ass...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605294/ https://www.ncbi.nlm.nih.gov/pubmed/34853721 http://dx.doi.org/10.1016/j.omtn.2021.10.025 |
_version_ | 1784602147627728896 |
---|---|
author | Chang, Yue Zhao, Yulu Wang, Liya Wu, Meijuan He, Chenglong Huang, Mengxi Lei, Zengjie Yang, Jiahe Han, Siqi Wang, Bibo Chen, Yanyan Liu, Chao Yu, Hongju Xue, Lijun Geng, Jian Chen, Yanan Dai, Tingting Ren, Lili Wang, Qian Liu, Xiaobei Chu, Xiaoyuan Chen, Cheng |
author_facet | Chang, Yue Zhao, Yulu Wang, Liya Wu, Meijuan He, Chenglong Huang, Mengxi Lei, Zengjie Yang, Jiahe Han, Siqi Wang, Bibo Chen, Yanyan Liu, Chao Yu, Hongju Xue, Lijun Geng, Jian Chen, Yanan Dai, Tingting Ren, Lili Wang, Qian Liu, Xiaobei Chu, Xiaoyuan Chen, Cheng |
author_sort | Chang, Yue |
collection | PubMed |
description | Dysregulated alternative splicing (AS) plays critical roles in driving cancer progression, and the underlying mechanisms remain largely unknown. Here, we demonstrated that PHF5A, a component of U2 small nuclear ribonucleoproteins, was frequently upregulated in colorectal cancer (CRC) samples and associated with poor prognosis. PHF5A promoted proliferation and metastasis of CRC cells in vitro and in vivo. Transcriptomic analysis identified PHF5A-regulated AS targets and pathways. Particularly, PHF5A induced TEAD2 exon 2 inclusion to activate YAP signaling, and interference of TEAD2-L partially reversed the PHF5A-mediated tumor progression. Pharmacological inhibition of PHF5A using pladienolide B had potent antitumor activity. Collectively, these data revealed the oncogenic role of PHF5A in CRC through regulating AS and established PHF5A as potential therapeutic target. |
format | Online Article Text |
id | pubmed-8605294 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-86052942021-11-30 PHF5A promotes colorectal cancerprogression by alternative splicing of TEAD2 Chang, Yue Zhao, Yulu Wang, Liya Wu, Meijuan He, Chenglong Huang, Mengxi Lei, Zengjie Yang, Jiahe Han, Siqi Wang, Bibo Chen, Yanyan Liu, Chao Yu, Hongju Xue, Lijun Geng, Jian Chen, Yanan Dai, Tingting Ren, Lili Wang, Qian Liu, Xiaobei Chu, Xiaoyuan Chen, Cheng Mol Ther Nucleic Acids Original Article Dysregulated alternative splicing (AS) plays critical roles in driving cancer progression, and the underlying mechanisms remain largely unknown. Here, we demonstrated that PHF5A, a component of U2 small nuclear ribonucleoproteins, was frequently upregulated in colorectal cancer (CRC) samples and associated with poor prognosis. PHF5A promoted proliferation and metastasis of CRC cells in vitro and in vivo. Transcriptomic analysis identified PHF5A-regulated AS targets and pathways. Particularly, PHF5A induced TEAD2 exon 2 inclusion to activate YAP signaling, and interference of TEAD2-L partially reversed the PHF5A-mediated tumor progression. Pharmacological inhibition of PHF5A using pladienolide B had potent antitumor activity. Collectively, these data revealed the oncogenic role of PHF5A in CRC through regulating AS and established PHF5A as potential therapeutic target. American Society of Gene & Cell Therapy 2021-11-03 /pmc/articles/PMC8605294/ /pubmed/34853721 http://dx.doi.org/10.1016/j.omtn.2021.10.025 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Chang, Yue Zhao, Yulu Wang, Liya Wu, Meijuan He, Chenglong Huang, Mengxi Lei, Zengjie Yang, Jiahe Han, Siqi Wang, Bibo Chen, Yanyan Liu, Chao Yu, Hongju Xue, Lijun Geng, Jian Chen, Yanan Dai, Tingting Ren, Lili Wang, Qian Liu, Xiaobei Chu, Xiaoyuan Chen, Cheng PHF5A promotes colorectal cancerprogression by alternative splicing of TEAD2 |
title | PHF5A promotes colorectal cancerprogression by alternative splicing of TEAD2 |
title_full | PHF5A promotes colorectal cancerprogression by alternative splicing of TEAD2 |
title_fullStr | PHF5A promotes colorectal cancerprogression by alternative splicing of TEAD2 |
title_full_unstemmed | PHF5A promotes colorectal cancerprogression by alternative splicing of TEAD2 |
title_short | PHF5A promotes colorectal cancerprogression by alternative splicing of TEAD2 |
title_sort | phf5a promotes colorectal cancerprogression by alternative splicing of tead2 |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605294/ https://www.ncbi.nlm.nih.gov/pubmed/34853721 http://dx.doi.org/10.1016/j.omtn.2021.10.025 |
work_keys_str_mv | AT changyue phf5apromotescolorectalcancerprogressionbyalternativesplicingoftead2 AT zhaoyulu phf5apromotescolorectalcancerprogressionbyalternativesplicingoftead2 AT wangliya phf5apromotescolorectalcancerprogressionbyalternativesplicingoftead2 AT wumeijuan phf5apromotescolorectalcancerprogressionbyalternativesplicingoftead2 AT hechenglong phf5apromotescolorectalcancerprogressionbyalternativesplicingoftead2 AT huangmengxi phf5apromotescolorectalcancerprogressionbyalternativesplicingoftead2 AT leizengjie phf5apromotescolorectalcancerprogressionbyalternativesplicingoftead2 AT yangjiahe phf5apromotescolorectalcancerprogressionbyalternativesplicingoftead2 AT hansiqi phf5apromotescolorectalcancerprogressionbyalternativesplicingoftead2 AT wangbibo phf5apromotescolorectalcancerprogressionbyalternativesplicingoftead2 AT chenyanyan phf5apromotescolorectalcancerprogressionbyalternativesplicingoftead2 AT liuchao phf5apromotescolorectalcancerprogressionbyalternativesplicingoftead2 AT yuhongju phf5apromotescolorectalcancerprogressionbyalternativesplicingoftead2 AT xuelijun phf5apromotescolorectalcancerprogressionbyalternativesplicingoftead2 AT gengjian phf5apromotescolorectalcancerprogressionbyalternativesplicingoftead2 AT chenyanan phf5apromotescolorectalcancerprogressionbyalternativesplicingoftead2 AT daitingting phf5apromotescolorectalcancerprogressionbyalternativesplicingoftead2 AT renlili phf5apromotescolorectalcancerprogressionbyalternativesplicingoftead2 AT wangqian phf5apromotescolorectalcancerprogressionbyalternativesplicingoftead2 AT liuxiaobei phf5apromotescolorectalcancerprogressionbyalternativesplicingoftead2 AT chuxiaoyuan phf5apromotescolorectalcancerprogressionbyalternativesplicingoftead2 AT chencheng phf5apromotescolorectalcancerprogressionbyalternativesplicingoftead2 |