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:	Yue Chang, Yulu Zhao, Liya Wang, Meijuan Wu, Chenglong He, Mengxi Huang, Zengjie Lei, Jiahe Yang, Siqi Han, Bibo Wang, Yanyan Chen, Chao Liu, Hongju Yu, Lijun Xue, Jian Geng, Yanan Chen, Tingting Dai, Lili Ren, Qian Wang, Xiaobei Liu, Xiaoyuan Chu, Cheng Chen
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	alternative splicing PHF5A colorectal cancer TEAD2 therapeutic target Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/6cfb8d68c577471dba8182838bbac540
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spelling	oai:doaj.org-article:6cfb8d68c577471dba8182838bbac5402021-11-20T05:05:33ZPHF5A promotes colorectal cancerprogression by alternative splicing of TEAD22162-253110.1016/j.omtn.2021.10.025https://doaj.org/article/6cfb8d68c577471dba8182838bbac5402021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2162253121002687https://doaj.org/toc/2162-2531Dysregulated 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.Yue ChangYulu ZhaoLiya WangMeijuan WuChenglong HeMengxi HuangZengjie LeiJiahe YangSiqi HanBibo WangYanyan ChenChao LiuHongju YuLijun XueJian GengYanan ChenTingting DaiLili RenQian WangXiaobei LiuXiaoyuan ChuCheng ChenElsevierarticlealternative splicingPHF5Acolorectal cancerTEAD2therapeutic targetTherapeutics. PharmacologyRM1-950ENMolecular Therapy: Nucleic Acids, Vol 26, Iss , Pp 1215-1227 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	alternative splicing PHF5A colorectal cancer TEAD2 therapeutic target Therapeutics. Pharmacology RM1-950
spellingShingle	alternative splicing PHF5A colorectal cancer TEAD2 therapeutic target Therapeutics. Pharmacology RM1-950 Yue Chang Yulu Zhao Liya Wang Meijuan Wu Chenglong He Mengxi Huang Zengjie Lei Jiahe Yang Siqi Han Bibo Wang Yanyan Chen Chao Liu Hongju Yu Lijun Xue Jian Geng Yanan Chen Tingting Dai Lili Ren Qian Wang Xiaobei Liu Xiaoyuan Chu Cheng Chen PHF5A promotes colorectal cancerprogression by alternative splicing of TEAD2
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	article
author	Yue Chang Yulu Zhao Liya Wang Meijuan Wu Chenglong He Mengxi Huang Zengjie Lei Jiahe Yang Siqi Han Bibo Wang Yanyan Chen Chao Liu Hongju Yu Lijun Xue Jian Geng Yanan Chen Tingting Dai Lili Ren Qian Wang Xiaobei Liu Xiaoyuan Chu Cheng Chen
author_facet	Yue Chang Yulu Zhao Liya Wang Meijuan Wu Chenglong He Mengxi Huang Zengjie Lei Jiahe Yang Siqi Han Bibo Wang Yanyan Chen Chao Liu Hongju Yu Lijun Xue Jian Geng Yanan Chen Tingting Dai Lili Ren Qian Wang Xiaobei Liu Xiaoyuan Chu Cheng Chen
author_sort	Yue Chang
title	PHF5A promotes colorectal cancerprogression by alternative splicing of TEAD2
title_short	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_sort	phf5a promotes colorectal cancerprogression by alternative splicing of tead2
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/6cfb8d68c577471dba8182838bbac540
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PHF5A promotes colorectal cancerprogression by alternative splicing of TEAD2

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