CSTF2 mediated mRNA N(6)-methyladenosine modification drives pancreatic ductal adenocarcinoma m(6)A subtypes

N(6)-methyladenosine (m(6)A) modification of gene transcripts plays critical roles in cancer. Here we report transcriptomic m(6)A profiling in 98 tissue samples from 65 individuals with pancreatic ductal adenocarcinoma (PDAC). We identify 17,996 m(6)A peaks with 195 hyper-methylated and 93 hypo-meth...

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Autores principales: Zheng, Yanfen, Li, Xingyang, Deng, Shuang, Zhao, Hongzhe, Ye, Ying, Zhang, Shaoping, Huang, Xudong, Bai, Ruihong, Zhuang, Lisha, Zhou, Quanbo, Li, Mei, Su, Jiachun, Li, Rui, Bao, Xiaoqiong, Zeng, Lingxing, Chen, Rufu, Zheng, Jian, Lin, Dongxin, He, Chuan, Zhang, Jialiang, Zuo, Zhixiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10564946/
https://www.ncbi.nlm.nih.gov/pubmed/37816727
http://dx.doi.org/10.1038/s41467-023-41861-y
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author Zheng, Yanfen
Li, Xingyang
Deng, Shuang
Zhao, Hongzhe
Ye, Ying
Zhang, Shaoping
Huang, Xudong
Bai, Ruihong
Zhuang, Lisha
Zhou, Quanbo
Li, Mei
Su, Jiachun
Li, Rui
Bao, Xiaoqiong
Zeng, Lingxing
Chen, Rufu
Zheng, Jian
Lin, Dongxin
He, Chuan
Zhang, Jialiang
Zuo, Zhixiang
author_facet Zheng, Yanfen
Li, Xingyang
Deng, Shuang
Zhao, Hongzhe
Ye, Ying
Zhang, Shaoping
Huang, Xudong
Bai, Ruihong
Zhuang, Lisha
Zhou, Quanbo
Li, Mei
Su, Jiachun
Li, Rui
Bao, Xiaoqiong
Zeng, Lingxing
Chen, Rufu
Zheng, Jian
Lin, Dongxin
He, Chuan
Zhang, Jialiang
Zuo, Zhixiang
author_sort Zheng, Yanfen
collection PubMed
description N(6)-methyladenosine (m(6)A) modification of gene transcripts plays critical roles in cancer. Here we report transcriptomic m(6)A profiling in 98 tissue samples from 65 individuals with pancreatic ductal adenocarcinoma (PDAC). We identify 17,996 m(6)A peaks with 195 hyper-methylated and 93 hypo-methylated in PDAC compared with adjacent normal tissues. The differential m(6)A modifications distinguish two PDAC subtypes with different prognosis outcomes. The formation of the two subtypes is driven by a newly identified m(6)A regulator CSTF2 that co-transcriptionally regulates m(6)A installation through slowing the RNA Pol II elongation rate during gene transcription. We find that most of the CSTF2-regulated m(6)As have positive effects on the RNA level of host genes, and CSTF2-regulated m(6)As are mainly recognized by IGF2BP2, an m(6)A reader that stabilizes mRNAs. These results provide a promising PDAC subtyping strategy and potential therapeutic targets for precision medicine of PDAC.
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spelling pubmed-105649462023-10-12 CSTF2 mediated mRNA N(6)-methyladenosine modification drives pancreatic ductal adenocarcinoma m(6)A subtypes Zheng, Yanfen Li, Xingyang Deng, Shuang Zhao, Hongzhe Ye, Ying Zhang, Shaoping Huang, Xudong Bai, Ruihong Zhuang, Lisha Zhou, Quanbo Li, Mei Su, Jiachun Li, Rui Bao, Xiaoqiong Zeng, Lingxing Chen, Rufu Zheng, Jian Lin, Dongxin He, Chuan Zhang, Jialiang Zuo, Zhixiang Nat Commun Article N(6)-methyladenosine (m(6)A) modification of gene transcripts plays critical roles in cancer. Here we report transcriptomic m(6)A profiling in 98 tissue samples from 65 individuals with pancreatic ductal adenocarcinoma (PDAC). We identify 17,996 m(6)A peaks with 195 hyper-methylated and 93 hypo-methylated in PDAC compared with adjacent normal tissues. The differential m(6)A modifications distinguish two PDAC subtypes with different prognosis outcomes. The formation of the two subtypes is driven by a newly identified m(6)A regulator CSTF2 that co-transcriptionally regulates m(6)A installation through slowing the RNA Pol II elongation rate during gene transcription. We find that most of the CSTF2-regulated m(6)As have positive effects on the RNA level of host genes, and CSTF2-regulated m(6)As are mainly recognized by IGF2BP2, an m(6)A reader that stabilizes mRNAs. These results provide a promising PDAC subtyping strategy and potential therapeutic targets for precision medicine of PDAC. Nature Publishing Group UK 2023-10-10 /pmc/articles/PMC10564946/ /pubmed/37816727 http://dx.doi.org/10.1038/s41467-023-41861-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zheng, Yanfen
Li, Xingyang
Deng, Shuang
Zhao, Hongzhe
Ye, Ying
Zhang, Shaoping
Huang, Xudong
Bai, Ruihong
Zhuang, Lisha
Zhou, Quanbo
Li, Mei
Su, Jiachun
Li, Rui
Bao, Xiaoqiong
Zeng, Lingxing
Chen, Rufu
Zheng, Jian
Lin, Dongxin
He, Chuan
Zhang, Jialiang
Zuo, Zhixiang
CSTF2 mediated mRNA N(6)-methyladenosine modification drives pancreatic ductal adenocarcinoma m(6)A subtypes
title CSTF2 mediated mRNA N(6)-methyladenosine modification drives pancreatic ductal adenocarcinoma m(6)A subtypes
title_full CSTF2 mediated mRNA N(6)-methyladenosine modification drives pancreatic ductal adenocarcinoma m(6)A subtypes
title_fullStr CSTF2 mediated mRNA N(6)-methyladenosine modification drives pancreatic ductal adenocarcinoma m(6)A subtypes
title_full_unstemmed CSTF2 mediated mRNA N(6)-methyladenosine modification drives pancreatic ductal adenocarcinoma m(6)A subtypes
title_short CSTF2 mediated mRNA N(6)-methyladenosine modification drives pancreatic ductal adenocarcinoma m(6)A subtypes
title_sort cstf2 mediated mrna n(6)-methyladenosine modification drives pancreatic ductal adenocarcinoma m(6)a subtypes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10564946/
https://www.ncbi.nlm.nih.gov/pubmed/37816727
http://dx.doi.org/10.1038/s41467-023-41861-y
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