Cargando…

Epigenetic regulation of EIF4A1 through DNA methylation and an oncogenic role of eIF4A1 through BRD2 signaling in prostate cancer

In prostate cancers, elongation initiation factor 4A1 (eIF4A1) supports an oncogenic translation program and is highly expressed, but its role remains elusive. By use of human specimens and cell models, we addressed the role of eIF4A1 in prostate cancer in vitro and in vivo. EIF4A1 expression, as de...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Chao, Leavenworth, Jonathan, Zhang, Chao, Liu, Zhichao, Yuan, Katherine Y., Wang, Yichun, Zhang, Guangxin, Wang, Shuaibin, Cui, Xuelian, Zhang, Yue, Bae, Sejong, Zhou, Jiangbing, Wang, Lizhong, Liu, Runhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9215223/
https://www.ncbi.nlm.nih.gov/pubmed/35361883
http://dx.doi.org/10.1038/s41388-022-02272-3
_version_ 1784731168318423040
author Wang, Chao
Leavenworth, Jonathan
Zhang, Chao
Liu, Zhichao
Yuan, Katherine Y.
Wang, Yichun
Zhang, Guangxin
Wang, Shuaibin
Cui, Xuelian
Zhang, Yue
Bae, Sejong
Zhou, Jiangbing
Wang, Lizhong
Liu, Runhua
author_facet Wang, Chao
Leavenworth, Jonathan
Zhang, Chao
Liu, Zhichao
Yuan, Katherine Y.
Wang, Yichun
Zhang, Guangxin
Wang, Shuaibin
Cui, Xuelian
Zhang, Yue
Bae, Sejong
Zhou, Jiangbing
Wang, Lizhong
Liu, Runhua
author_sort Wang, Chao
collection PubMed
description In prostate cancers, elongation initiation factor 4A1 (eIF4A1) supports an oncogenic translation program and is highly expressed, but its role remains elusive. By use of human specimens and cell models, we addressed the role of eIF4A1 in prostate cancer in vitro and in vivo. EIF4A1 expression, as determined by mRNA and protein levels, was higher in primary prostate cancers relative to normal prostate tissue. Also, for primary prostate cancers, elevated mRNA levels of EIF4A1 correlated with DNA hypomethylation levels in the CpG-rich island of EIF4A1. Using a DNMT3a CRISPR-Cas9-based tool for specific targeting of DNA methylation, we characterized, in human prostate cancer cells, the epigenetic regulation of EIF4A1 transcripts through DNA methylation in the CpG-rich island of EIF4A1. Next, we investigated the oncogenic effect of EIF4A1 on cancer cell proliferation in vitro and tumor growth in vivo. For prostate cancer cells, EIF4A1 heterozygous knockout or knockdown inhibited protein translation and tumor growth. In addition, using RNA immunoprecipitation with RNA sequencing, we discovered the eIF4A1-mediated translational regulation of the oncogene BRD2, which contains the most enriched eIF4A1-binding motifs in its 5’ untranslated region, establishing an eIF4A1-BRD2 axis for oncogenic translation. Finally, we found a positive correlation between expression levels of eIF4A1 and BRD2 in primary prostate cancers. Our results demonstrate, for prostate cancer cells, epigenetic regulation of EIF4A1 transcripts through DNA methylation and an oncogenic roles of eIF4A1 through BRD2 signaling.
format Online
Article
Text
id pubmed-9215223
institution National Center for Biotechnology Information
language English
publishDate 2022
record_format MEDLINE/PubMed
spelling pubmed-92152232022-09-30 Epigenetic regulation of EIF4A1 through DNA methylation and an oncogenic role of eIF4A1 through BRD2 signaling in prostate cancer Wang, Chao Leavenworth, Jonathan Zhang, Chao Liu, Zhichao Yuan, Katherine Y. Wang, Yichun Zhang, Guangxin Wang, Shuaibin Cui, Xuelian Zhang, Yue Bae, Sejong Zhou, Jiangbing Wang, Lizhong Liu, Runhua Oncogene Article In prostate cancers, elongation initiation factor 4A1 (eIF4A1) supports an oncogenic translation program and is highly expressed, but its role remains elusive. By use of human specimens and cell models, we addressed the role of eIF4A1 in prostate cancer in vitro and in vivo. EIF4A1 expression, as determined by mRNA and protein levels, was higher in primary prostate cancers relative to normal prostate tissue. Also, for primary prostate cancers, elevated mRNA levels of EIF4A1 correlated with DNA hypomethylation levels in the CpG-rich island of EIF4A1. Using a DNMT3a CRISPR-Cas9-based tool for specific targeting of DNA methylation, we characterized, in human prostate cancer cells, the epigenetic regulation of EIF4A1 transcripts through DNA methylation in the CpG-rich island of EIF4A1. Next, we investigated the oncogenic effect of EIF4A1 on cancer cell proliferation in vitro and tumor growth in vivo. For prostate cancer cells, EIF4A1 heterozygous knockout or knockdown inhibited protein translation and tumor growth. In addition, using RNA immunoprecipitation with RNA sequencing, we discovered the eIF4A1-mediated translational regulation of the oncogene BRD2, which contains the most enriched eIF4A1-binding motifs in its 5’ untranslated region, establishing an eIF4A1-BRD2 axis for oncogenic translation. Finally, we found a positive correlation between expression levels of eIF4A1 and BRD2 in primary prostate cancers. Our results demonstrate, for prostate cancer cells, epigenetic regulation of EIF4A1 transcripts through DNA methylation and an oncogenic roles of eIF4A1 through BRD2 signaling. 2022-05 2022-03-31 /pmc/articles/PMC9215223/ /pubmed/35361883 http://dx.doi.org/10.1038/s41388-022-02272-3 Text en http://www.nature.com/authors/editorial_policies/license.html#termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Wang, Chao
Leavenworth, Jonathan
Zhang, Chao
Liu, Zhichao
Yuan, Katherine Y.
Wang, Yichun
Zhang, Guangxin
Wang, Shuaibin
Cui, Xuelian
Zhang, Yue
Bae, Sejong
Zhou, Jiangbing
Wang, Lizhong
Liu, Runhua
Epigenetic regulation of EIF4A1 through DNA methylation and an oncogenic role of eIF4A1 through BRD2 signaling in prostate cancer
title Epigenetic regulation of EIF4A1 through DNA methylation and an oncogenic role of eIF4A1 through BRD2 signaling in prostate cancer
title_full Epigenetic regulation of EIF4A1 through DNA methylation and an oncogenic role of eIF4A1 through BRD2 signaling in prostate cancer
title_fullStr Epigenetic regulation of EIF4A1 through DNA methylation and an oncogenic role of eIF4A1 through BRD2 signaling in prostate cancer
title_full_unstemmed Epigenetic regulation of EIF4A1 through DNA methylation and an oncogenic role of eIF4A1 through BRD2 signaling in prostate cancer
title_short Epigenetic regulation of EIF4A1 through DNA methylation and an oncogenic role of eIF4A1 through BRD2 signaling in prostate cancer
title_sort epigenetic regulation of eif4a1 through dna methylation and an oncogenic role of eif4a1 through brd2 signaling in prostate cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9215223/
https://www.ncbi.nlm.nih.gov/pubmed/35361883
http://dx.doi.org/10.1038/s41388-022-02272-3
work_keys_str_mv AT wangchao epigeneticregulationofeif4a1throughdnamethylationandanoncogenicroleofeif4a1throughbrd2signalinginprostatecancer
AT leavenworthjonathan epigeneticregulationofeif4a1throughdnamethylationandanoncogenicroleofeif4a1throughbrd2signalinginprostatecancer
AT zhangchao epigeneticregulationofeif4a1throughdnamethylationandanoncogenicroleofeif4a1throughbrd2signalinginprostatecancer
AT liuzhichao epigeneticregulationofeif4a1throughdnamethylationandanoncogenicroleofeif4a1throughbrd2signalinginprostatecancer
AT yuankatheriney epigeneticregulationofeif4a1throughdnamethylationandanoncogenicroleofeif4a1throughbrd2signalinginprostatecancer
AT wangyichun epigeneticregulationofeif4a1throughdnamethylationandanoncogenicroleofeif4a1throughbrd2signalinginprostatecancer
AT zhangguangxin epigeneticregulationofeif4a1throughdnamethylationandanoncogenicroleofeif4a1throughbrd2signalinginprostatecancer
AT wangshuaibin epigeneticregulationofeif4a1throughdnamethylationandanoncogenicroleofeif4a1throughbrd2signalinginprostatecancer
AT cuixuelian epigeneticregulationofeif4a1throughdnamethylationandanoncogenicroleofeif4a1throughbrd2signalinginprostatecancer
AT zhangyue epigeneticregulationofeif4a1throughdnamethylationandanoncogenicroleofeif4a1throughbrd2signalinginprostatecancer
AT baesejong epigeneticregulationofeif4a1throughdnamethylationandanoncogenicroleofeif4a1throughbrd2signalinginprostatecancer
AT zhoujiangbing epigeneticregulationofeif4a1throughdnamethylationandanoncogenicroleofeif4a1throughbrd2signalinginprostatecancer
AT wanglizhong epigeneticregulationofeif4a1throughdnamethylationandanoncogenicroleofeif4a1throughbrd2signalinginprostatecancer
AT liurunhua epigeneticregulationofeif4a1throughdnamethylationandanoncogenicroleofeif4a1throughbrd2signalinginprostatecancer