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Cleavage and Polyadenylation Specific Factor 1 Promotes Tumor Progression via Alternative Polyadenylation and Splicing in Hepatocellular Carcinoma

Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism required for cleavage and polyadenylation (CPA) of the 3′ untranslated region (3′ UTR) of mRNAs. Several aberrant APA events have been reported in hepatocellular carcinoma (HCC). However, the regulatory mecha...

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Autores principales: Chen, Shi-lu, Zhu, Zhong-xu, Yang, Xia, Liu, Li-li, He, Yang-fan, Yang, Ming-ming, Guan, Xin-yuan, Wang, Xin, Yun, Jing-ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969726/
https://www.ncbi.nlm.nih.gov/pubmed/33748106
http://dx.doi.org/10.3389/fcell.2021.616835
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author Chen, Shi-lu
Zhu, Zhong-xu
Yang, Xia
Liu, Li-li
He, Yang-fan
Yang, Ming-ming
Guan, Xin-yuan
Wang, Xin
Yun, Jing-ping
author_facet Chen, Shi-lu
Zhu, Zhong-xu
Yang, Xia
Liu, Li-li
He, Yang-fan
Yang, Ming-ming
Guan, Xin-yuan
Wang, Xin
Yun, Jing-ping
author_sort Chen, Shi-lu
collection PubMed
description Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism required for cleavage and polyadenylation (CPA) of the 3′ untranslated region (3′ UTR) of mRNAs. Several aberrant APA events have been reported in hepatocellular carcinoma (HCC). However, the regulatory mechanisms underlying APA remain unclear. In this study, we found that the expression of cleavage and polyadenylation specific factor 1 (CPSF1), a major component of the CPA complex, was significantly increased in HCC tissues and correlated with unfavorable survival outcomes. Knockdown of CPSF1 inhibited HCC cell proliferation and migration, whereas overexpression of CPSF1 caused the opposite effect. Based on integrative analysis of Iso-Seq and RNA-seq data from HepG2.2.15 cells, we identified a series of transcripts with differential 3′ UTR lengths following the knockdown of CPSF1. These transcripts were related to the biological functions of gene transcription, cytoskeleton maintenance, and endomembrane system transportation. Moreover, knockdown of CPSF1 induced an increase in alternative splicing (AS) events in addition to APA. Taken together, this study provides new insights into our understanding of the post-transcriptional regulatory mechanisms in HCC and implies that CPSF1 may be a potential prognostic biomarker and therapeutic target for HCC.
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spelling pubmed-79697262021-03-19 Cleavage and Polyadenylation Specific Factor 1 Promotes Tumor Progression via Alternative Polyadenylation and Splicing in Hepatocellular Carcinoma Chen, Shi-lu Zhu, Zhong-xu Yang, Xia Liu, Li-li He, Yang-fan Yang, Ming-ming Guan, Xin-yuan Wang, Xin Yun, Jing-ping Front Cell Dev Biol Cell and Developmental Biology Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism required for cleavage and polyadenylation (CPA) of the 3′ untranslated region (3′ UTR) of mRNAs. Several aberrant APA events have been reported in hepatocellular carcinoma (HCC). However, the regulatory mechanisms underlying APA remain unclear. In this study, we found that the expression of cleavage and polyadenylation specific factor 1 (CPSF1), a major component of the CPA complex, was significantly increased in HCC tissues and correlated with unfavorable survival outcomes. Knockdown of CPSF1 inhibited HCC cell proliferation and migration, whereas overexpression of CPSF1 caused the opposite effect. Based on integrative analysis of Iso-Seq and RNA-seq data from HepG2.2.15 cells, we identified a series of transcripts with differential 3′ UTR lengths following the knockdown of CPSF1. These transcripts were related to the biological functions of gene transcription, cytoskeleton maintenance, and endomembrane system transportation. Moreover, knockdown of CPSF1 induced an increase in alternative splicing (AS) events in addition to APA. Taken together, this study provides new insights into our understanding of the post-transcriptional regulatory mechanisms in HCC and implies that CPSF1 may be a potential prognostic biomarker and therapeutic target for HCC. Frontiers Media S.A. 2021-03-04 /pmc/articles/PMC7969726/ /pubmed/33748106 http://dx.doi.org/10.3389/fcell.2021.616835 Text en Copyright © 2021 Chen, Zhu, Yang, Liu, He, Yang, Guan, Wang and Yun. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Chen, Shi-lu
Zhu, Zhong-xu
Yang, Xia
Liu, Li-li
He, Yang-fan
Yang, Ming-ming
Guan, Xin-yuan
Wang, Xin
Yun, Jing-ping
Cleavage and Polyadenylation Specific Factor 1 Promotes Tumor Progression via Alternative Polyadenylation and Splicing in Hepatocellular Carcinoma
title Cleavage and Polyadenylation Specific Factor 1 Promotes Tumor Progression via Alternative Polyadenylation and Splicing in Hepatocellular Carcinoma
title_full Cleavage and Polyadenylation Specific Factor 1 Promotes Tumor Progression via Alternative Polyadenylation and Splicing in Hepatocellular Carcinoma
title_fullStr Cleavage and Polyadenylation Specific Factor 1 Promotes Tumor Progression via Alternative Polyadenylation and Splicing in Hepatocellular Carcinoma
title_full_unstemmed Cleavage and Polyadenylation Specific Factor 1 Promotes Tumor Progression via Alternative Polyadenylation and Splicing in Hepatocellular Carcinoma
title_short Cleavage and Polyadenylation Specific Factor 1 Promotes Tumor Progression via Alternative Polyadenylation and Splicing in Hepatocellular Carcinoma
title_sort cleavage and polyadenylation specific factor 1 promotes tumor progression via alternative polyadenylation and splicing in hepatocellular carcinoma
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969726/
https://www.ncbi.nlm.nih.gov/pubmed/33748106
http://dx.doi.org/10.3389/fcell.2021.616835
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