RNA m(6)A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail

N6-Methyladenosine (m(6)A) modification has been implicated in the progression of several cancers. We reveal that during epithelial-mesenchymal transition (EMT), one important step for cancer cell metastasis, m(6)A modification of mRNAs increases in cancer cells. Deletion of methyltransferase-like 3...

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Autores principales: Lin, Xinyao, Chai, Guoshi, Wu, Yingmin, Li, Jiexin, Chen, Feng, Liu, Jianzhao, Luo, Guanzheng, Tauler, Jordi, Du, Jun, Lin, Shuibin, He, Chuan, Wang, Hongsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502834/
https://www.ncbi.nlm.nih.gov/pubmed/31061416
http://dx.doi.org/10.1038/s41467-019-09865-9
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author Lin, Xinyao
Chai, Guoshi
Wu, Yingmin
Li, Jiexin
Chen, Feng
Liu, Jianzhao
Luo, Guanzheng
Tauler, Jordi
Du, Jun
Lin, Shuibin
He, Chuan
Wang, Hongsheng
author_facet Lin, Xinyao
Chai, Guoshi
Wu, Yingmin
Li, Jiexin
Chen, Feng
Liu, Jianzhao
Luo, Guanzheng
Tauler, Jordi
Du, Jun
Lin, Shuibin
He, Chuan
Wang, Hongsheng
author_sort Lin, Xinyao
collection PubMed
description N6-Methyladenosine (m(6)A) modification has been implicated in the progression of several cancers. We reveal that during epithelial-mesenchymal transition (EMT), one important step for cancer cell metastasis, m(6)A modification of mRNAs increases in cancer cells. Deletion of methyltransferase-like 3 (METTL3) down-regulates m(6)A, impairs the migration, invasion and EMT of cancer cells both in vitro and in vivo. m(6)A-sequencing and functional studies confirm that Snail, a key transcription factor of EMT, is involved in m(6)A-regulated EMT. m(6)A in Snail CDS, but not 3’UTR, triggers polysome-mediated translation of Snail mRNA in cancer cells. Loss and gain functional studies confirm that YTHDF1 mediates m(6)A-increased translation of Snail mRNA. Moreover, the upregulation of METTL3 and YTHDF1 act as adverse prognosis factors for overall survival (OS) rate of liver cancer patients. Our study highlights the critical roles of m(6)A on regulation of EMT in cancer cells and translation of Snail during this process.
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spelling pubmed-65028342019-05-08 RNA m(6)A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail Lin, Xinyao Chai, Guoshi Wu, Yingmin Li, Jiexin Chen, Feng Liu, Jianzhao Luo, Guanzheng Tauler, Jordi Du, Jun Lin, Shuibin He, Chuan Wang, Hongsheng Nat Commun Article N6-Methyladenosine (m(6)A) modification has been implicated in the progression of several cancers. We reveal that during epithelial-mesenchymal transition (EMT), one important step for cancer cell metastasis, m(6)A modification of mRNAs increases in cancer cells. Deletion of methyltransferase-like 3 (METTL3) down-regulates m(6)A, impairs the migration, invasion and EMT of cancer cells both in vitro and in vivo. m(6)A-sequencing and functional studies confirm that Snail, a key transcription factor of EMT, is involved in m(6)A-regulated EMT. m(6)A in Snail CDS, but not 3’UTR, triggers polysome-mediated translation of Snail mRNA in cancer cells. Loss and gain functional studies confirm that YTHDF1 mediates m(6)A-increased translation of Snail mRNA. Moreover, the upregulation of METTL3 and YTHDF1 act as adverse prognosis factors for overall survival (OS) rate of liver cancer patients. Our study highlights the critical roles of m(6)A on regulation of EMT in cancer cells and translation of Snail during this process. Nature Publishing Group UK 2019-05-06 /pmc/articles/PMC6502834/ /pubmed/31061416 http://dx.doi.org/10.1038/s41467-019-09865-9 Text en © The Author(s) 2019 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lin, Xinyao
Chai, Guoshi
Wu, Yingmin
Li, Jiexin
Chen, Feng
Liu, Jianzhao
Luo, Guanzheng
Tauler, Jordi
Du, Jun
Lin, Shuibin
He, Chuan
Wang, Hongsheng
RNA m(6)A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail
title RNA m(6)A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail
title_full RNA m(6)A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail
title_fullStr RNA m(6)A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail
title_full_unstemmed RNA m(6)A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail
title_short RNA m(6)A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail
title_sort rna m(6)a methylation regulates the epithelial mesenchymal transition of cancer cells and translation of snail
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502834/
https://www.ncbi.nlm.nih.gov/pubmed/31061416
http://dx.doi.org/10.1038/s41467-019-09865-9
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