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Downregulation of m(6)A Reader YTHDC2 Promotes the Proliferation and Migration of Malignant Lung Cells via CYLD/NF-κB Pathway
Lung cancer is one of the most common types of carcinoma worldwide. Cigarette smoking is considered the leading cause of lung cancer. Aberrant expression of several YT521-B homology (YTH) family proteins has been reported to be closely associated with multiple cancer types. The present study aims to...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Ivyspring International Publisher
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315025/ https://www.ncbi.nlm.nih.gov/pubmed/34326699 http://dx.doi.org/10.7150/ijbs.58514 |
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author | Wang, Jin Tan, Lirong Jia, Beibei Yu, Xiaofan Yao, Ruixin OUYang, Nan Yu, Xueting Cao, Xiyuan Tong, Jian Chen, Tao Chen, Rui Li, Jianxiang |
author_facet | Wang, Jin Tan, Lirong Jia, Beibei Yu, Xiaofan Yao, Ruixin OUYang, Nan Yu, Xueting Cao, Xiyuan Tong, Jian Chen, Tao Chen, Rui Li, Jianxiang |
author_sort | Wang, Jin |
collection | PubMed |
description | Lung cancer is one of the most common types of carcinoma worldwide. Cigarette smoking is considered the leading cause of lung cancer. Aberrant expression of several YT521-B homology (YTH) family proteins has been reported to be closely associated with multiple cancer types. The present study aims to evaluate the function and regulatory mechanisms of the N6-methyladenosine (m(6)A) reader protein YTH domain containing 2 (YTHDC2) by in vitro, in vivo and bioinformatics analyses. The results revealed that YTHDC2 was reduced in lung cancer and cigarette smoke-exposed cells. Notably, bioinformatics and tissue arrays analysis demonstrated that decreased YTHDC2 was highly associated with smoking history, pathological stage, invasion depth, lymph node metastasis and poor outcomes. The in vivo and in vitro studies revealed that YTHDC2 overexpression inhibited the proliferation and migration of lung cancer cells as well as tumor growth in nude mice. Furthermore, YTHDC2 decreased expression was modulated by copy number deletion in lung cancer. Importantly, the cylindromatosis (CYLD)/NF-κB pathways were confirmed as the downstream signaling of YTHDC2, and this axis was mediated by m(6)A modification. The present results indicated that smoking-related downregulation of YTHDC2 was associated with enhanced proliferation and migration in lung cancer cells, and appeared to be regulated by DNA copy number variation. Importantly, YTHDC2 functions as a tumor suppressor through the CYLD/NF-κB signaling pathway, which is mediated by m(6)A modification. |
format | Online Article Text |
id | pubmed-8315025 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-83150252021-07-28 Downregulation of m(6)A Reader YTHDC2 Promotes the Proliferation and Migration of Malignant Lung Cells via CYLD/NF-κB Pathway Wang, Jin Tan, Lirong Jia, Beibei Yu, Xiaofan Yao, Ruixin OUYang, Nan Yu, Xueting Cao, Xiyuan Tong, Jian Chen, Tao Chen, Rui Li, Jianxiang Int J Biol Sci Research Paper Lung cancer is one of the most common types of carcinoma worldwide. Cigarette smoking is considered the leading cause of lung cancer. Aberrant expression of several YT521-B homology (YTH) family proteins has been reported to be closely associated with multiple cancer types. The present study aims to evaluate the function and regulatory mechanisms of the N6-methyladenosine (m(6)A) reader protein YTH domain containing 2 (YTHDC2) by in vitro, in vivo and bioinformatics analyses. The results revealed that YTHDC2 was reduced in lung cancer and cigarette smoke-exposed cells. Notably, bioinformatics and tissue arrays analysis demonstrated that decreased YTHDC2 was highly associated with smoking history, pathological stage, invasion depth, lymph node metastasis and poor outcomes. The in vivo and in vitro studies revealed that YTHDC2 overexpression inhibited the proliferation and migration of lung cancer cells as well as tumor growth in nude mice. Furthermore, YTHDC2 decreased expression was modulated by copy number deletion in lung cancer. Importantly, the cylindromatosis (CYLD)/NF-κB pathways were confirmed as the downstream signaling of YTHDC2, and this axis was mediated by m(6)A modification. The present results indicated that smoking-related downregulation of YTHDC2 was associated with enhanced proliferation and migration in lung cancer cells, and appeared to be regulated by DNA copy number variation. Importantly, YTHDC2 functions as a tumor suppressor through the CYLD/NF-κB signaling pathway, which is mediated by m(6)A modification. Ivyspring International Publisher 2021-06-22 /pmc/articles/PMC8315025/ /pubmed/34326699 http://dx.doi.org/10.7150/ijbs.58514 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Wang, Jin Tan, Lirong Jia, Beibei Yu, Xiaofan Yao, Ruixin OUYang, Nan Yu, Xueting Cao, Xiyuan Tong, Jian Chen, Tao Chen, Rui Li, Jianxiang Downregulation of m(6)A Reader YTHDC2 Promotes the Proliferation and Migration of Malignant Lung Cells via CYLD/NF-κB Pathway |
title | Downregulation of m(6)A Reader YTHDC2 Promotes the Proliferation and Migration of Malignant Lung Cells via CYLD/NF-κB Pathway |
title_full | Downregulation of m(6)A Reader YTHDC2 Promotes the Proliferation and Migration of Malignant Lung Cells via CYLD/NF-κB Pathway |
title_fullStr | Downregulation of m(6)A Reader YTHDC2 Promotes the Proliferation and Migration of Malignant Lung Cells via CYLD/NF-κB Pathway |
title_full_unstemmed | Downregulation of m(6)A Reader YTHDC2 Promotes the Proliferation and Migration of Malignant Lung Cells via CYLD/NF-κB Pathway |
title_short | Downregulation of m(6)A Reader YTHDC2 Promotes the Proliferation and Migration of Malignant Lung Cells via CYLD/NF-κB Pathway |
title_sort | downregulation of m(6)a reader ythdc2 promotes the proliferation and migration of malignant lung cells via cyld/nf-κb pathway |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315025/ https://www.ncbi.nlm.nih.gov/pubmed/34326699 http://dx.doi.org/10.7150/ijbs.58514 |
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