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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...

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Autores principales: 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
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
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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.
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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
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