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m1A Regulated Genes Modulate PI3K/AKT/mTOR and ErbB Pathways in Gastrointestinal Cancer

BACKGROUND: Gene expression can be posttranscriptionally regulated by a complex network of proteins. N1-methyladenosine (m1A) is a newly validated RNA modification. However, little is known about both its influence and biogenesis in tumor development. METHODS: This study analyzed TCGA data of patien...

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Autores principales: Zhao, Yueshui, Zhao, Qijie, Kaboli, Parham Jabbarzadeh, Shen, Jing, Li, Mingxing, Wu, Xu, Yin, Jianhua, Zhang, Hanyu, Wu, Yuanlin, Lin, Ling, Zhang, Lingling, Wan, Lin, Wen, Qinglian, Li, Xiang, Cho, Chi Hin, Yi, Tao, Li, Jing, Xiao, Zhangang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661385/
https://www.ncbi.nlm.nih.gov/pubmed/31352195
http://dx.doi.org/10.1016/j.tranon.2019.06.007
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author Zhao, Yueshui
Zhao, Qijie
Kaboli, Parham Jabbarzadeh
Shen, Jing
Li, Mingxing
Wu, Xu
Yin, Jianhua
Zhang, Hanyu
Wu, Yuanlin
Lin, Ling
Zhang, Lingling
Wan, Lin
Wen, Qinglian
Li, Xiang
Cho, Chi Hin
Yi, Tao
Li, Jing
Xiao, Zhangang
author_facet Zhao, Yueshui
Zhao, Qijie
Kaboli, Parham Jabbarzadeh
Shen, Jing
Li, Mingxing
Wu, Xu
Yin, Jianhua
Zhang, Hanyu
Wu, Yuanlin
Lin, Ling
Zhang, Lingling
Wan, Lin
Wen, Qinglian
Li, Xiang
Cho, Chi Hin
Yi, Tao
Li, Jing
Xiao, Zhangang
author_sort Zhao, Yueshui
collection PubMed
description BACKGROUND: Gene expression can be posttranscriptionally regulated by a complex network of proteins. N1-methyladenosine (m1A) is a newly validated RNA modification. However, little is known about both its influence and biogenesis in tumor development. METHODS: This study analyzed TCGA data of patients with five kinds of gastrointestinal (GI) cancers. Using data from cBioPortal, molecular features of the nine known m1A-related enzymes in GI cancers were investigated. Using a variety of bioinformatics approach, the impact of m1A regulators on its downstream signaling pathway was studied. To further confirm this regulation, the effect of m1A writer ALKBH3 knockdown was studied using RNA-seq data from published database. RESULTS: Dysregulation and multiple types of genetic alteration of putative m1A-related enzymes in tumor samples were observed. The ErbB and mTOR pathways with ErbB2, mTOR, and AKT1S1 hub genes were identified as being regulated by m1A-related enzymes. The expression of both ErbB2 and AKT1S1 was decreased after m1A writer ALKBH3 knockdown. Furthermore, Gene Ontology analysis revealed that m1A downstream genes were associated with cell proliferation, and the results showed that m1A genes are reliably linked to mTOR. CONCLUSION: This study demonstrated for the first time the dysregulation of m1A regulators in GI cancer and its signaling pathways and will contribute to the understanding of RNA modification in cancer.
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spelling pubmed-66613852019-08-01 m1A Regulated Genes Modulate PI3K/AKT/mTOR and ErbB Pathways in Gastrointestinal Cancer Zhao, Yueshui Zhao, Qijie Kaboli, Parham Jabbarzadeh Shen, Jing Li, Mingxing Wu, Xu Yin, Jianhua Zhang, Hanyu Wu, Yuanlin Lin, Ling Zhang, Lingling Wan, Lin Wen, Qinglian Li, Xiang Cho, Chi Hin Yi, Tao Li, Jing Xiao, Zhangang Transl Oncol Original article BACKGROUND: Gene expression can be posttranscriptionally regulated by a complex network of proteins. N1-methyladenosine (m1A) is a newly validated RNA modification. However, little is known about both its influence and biogenesis in tumor development. METHODS: This study analyzed TCGA data of patients with five kinds of gastrointestinal (GI) cancers. Using data from cBioPortal, molecular features of the nine known m1A-related enzymes in GI cancers were investigated. Using a variety of bioinformatics approach, the impact of m1A regulators on its downstream signaling pathway was studied. To further confirm this regulation, the effect of m1A writer ALKBH3 knockdown was studied using RNA-seq data from published database. RESULTS: Dysregulation and multiple types of genetic alteration of putative m1A-related enzymes in tumor samples were observed. The ErbB and mTOR pathways with ErbB2, mTOR, and AKT1S1 hub genes were identified as being regulated by m1A-related enzymes. The expression of both ErbB2 and AKT1S1 was decreased after m1A writer ALKBH3 knockdown. Furthermore, Gene Ontology analysis revealed that m1A downstream genes were associated with cell proliferation, and the results showed that m1A genes are reliably linked to mTOR. CONCLUSION: This study demonstrated for the first time the dysregulation of m1A regulators in GI cancer and its signaling pathways and will contribute to the understanding of RNA modification in cancer. Neoplasia Press 2019-07-25 /pmc/articles/PMC6661385/ /pubmed/31352195 http://dx.doi.org/10.1016/j.tranon.2019.06.007 Text en © 2019 The Authors http://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
Zhao, Yueshui
Zhao, Qijie
Kaboli, Parham Jabbarzadeh
Shen, Jing
Li, Mingxing
Wu, Xu
Yin, Jianhua
Zhang, Hanyu
Wu, Yuanlin
Lin, Ling
Zhang, Lingling
Wan, Lin
Wen, Qinglian
Li, Xiang
Cho, Chi Hin
Yi, Tao
Li, Jing
Xiao, Zhangang
m1A Regulated Genes Modulate PI3K/AKT/mTOR and ErbB Pathways in Gastrointestinal Cancer
title m1A Regulated Genes Modulate PI3K/AKT/mTOR and ErbB Pathways in Gastrointestinal Cancer
title_full m1A Regulated Genes Modulate PI3K/AKT/mTOR and ErbB Pathways in Gastrointestinal Cancer
title_fullStr m1A Regulated Genes Modulate PI3K/AKT/mTOR and ErbB Pathways in Gastrointestinal Cancer
title_full_unstemmed m1A Regulated Genes Modulate PI3K/AKT/mTOR and ErbB Pathways in Gastrointestinal Cancer
title_short m1A Regulated Genes Modulate PI3K/AKT/mTOR and ErbB Pathways in Gastrointestinal Cancer
title_sort m1a regulated genes modulate pi3k/akt/mtor and erbb pathways in gastrointestinal cancer
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661385/
https://www.ncbi.nlm.nih.gov/pubmed/31352195
http://dx.doi.org/10.1016/j.tranon.2019.06.007
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