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METTL3‐mediated m6A mRNA contributes to the resistance of carbon‐ion radiotherapy in non‐small‐cell lung cancer

Lung cancer is one of the leading causes of death among cancer patients worldwide. Carbon‐ion radiotherapy is a radical nonsurgical treatment with high local control rates and no serious adverse events. N6‐methyladenosine (m6A) modification is one of the most common chemical modifications in eukaryo...

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Autores principales: Xu, Xiaofeng, Zhang, Peiru, Huang, Yangle, Shi, Weizhong, Mao, Jingfang, Ma, Ningyi, Kong, Lin, Guo, Lin, Liu, Jinlong, Chen, Jian, Lu, Renquan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9807515/
https://www.ncbi.nlm.nih.gov/pubmed/36114749
http://dx.doi.org/10.1111/cas.15590
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author Xu, Xiaofeng
Zhang, Peiru
Huang, Yangle
Shi, Weizhong
Mao, Jingfang
Ma, Ningyi
Kong, Lin
Guo, Lin
Liu, Jinlong
Chen, Jian
Lu, Renquan
author_facet Xu, Xiaofeng
Zhang, Peiru
Huang, Yangle
Shi, Weizhong
Mao, Jingfang
Ma, Ningyi
Kong, Lin
Guo, Lin
Liu, Jinlong
Chen, Jian
Lu, Renquan
author_sort Xu, Xiaofeng
collection PubMed
description Lung cancer is one of the leading causes of death among cancer patients worldwide. Carbon‐ion radiotherapy is a radical nonsurgical treatment with high local control rates and no serious adverse events. N6‐methyladenosine (m6A) modification is one of the most common chemical modifications in eukaryotic messenger RNA (mRNA) and has important effects on the stability, splicing, and translation of mRNAs. Recently, the regulatory role of m6A in tumorigenesis has been recognized more and more. However, the dysregulation of m6A and its role in carbon‐ion radiotherapy of non‐small‐cell lung cancer (NSCLC) remains unclear. In this study, we found that the level of methyltransferase‐like 3 (METTL3) and its mediated m6A modification were elevated in NSCLC cells with carbon‐ion radiotherapy. Knockdown of METTL3 in NSCLC cells impaired proliferation, migration, and invasion in vitro and in vivo. Moreover, we found that METTL3‐mediated m6A modification of mRNA inhibited the decay of H2A histone family member X (H2AX) mRNA and enhanced its expression, which led to enhanced DNA damage repair and cell survival.
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spelling pubmed-98075152023-01-04 METTL3‐mediated m6A mRNA contributes to the resistance of carbon‐ion radiotherapy in non‐small‐cell lung cancer Xu, Xiaofeng Zhang, Peiru Huang, Yangle Shi, Weizhong Mao, Jingfang Ma, Ningyi Kong, Lin Guo, Lin Liu, Jinlong Chen, Jian Lu, Renquan Cancer Sci Original Articles Lung cancer is one of the leading causes of death among cancer patients worldwide. Carbon‐ion radiotherapy is a radical nonsurgical treatment with high local control rates and no serious adverse events. N6‐methyladenosine (m6A) modification is one of the most common chemical modifications in eukaryotic messenger RNA (mRNA) and has important effects on the stability, splicing, and translation of mRNAs. Recently, the regulatory role of m6A in tumorigenesis has been recognized more and more. However, the dysregulation of m6A and its role in carbon‐ion radiotherapy of non‐small‐cell lung cancer (NSCLC) remains unclear. In this study, we found that the level of methyltransferase‐like 3 (METTL3) and its mediated m6A modification were elevated in NSCLC cells with carbon‐ion radiotherapy. Knockdown of METTL3 in NSCLC cells impaired proliferation, migration, and invasion in vitro and in vivo. Moreover, we found that METTL3‐mediated m6A modification of mRNA inhibited the decay of H2A histone family member X (H2AX) mRNA and enhanced its expression, which led to enhanced DNA damage repair and cell survival. John Wiley and Sons Inc. 2022-10-09 /pmc/articles/PMC9807515/ /pubmed/36114749 http://dx.doi.org/10.1111/cas.15590 Text en © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Xu, Xiaofeng
Zhang, Peiru
Huang, Yangle
Shi, Weizhong
Mao, Jingfang
Ma, Ningyi
Kong, Lin
Guo, Lin
Liu, Jinlong
Chen, Jian
Lu, Renquan
METTL3‐mediated m6A mRNA contributes to the resistance of carbon‐ion radiotherapy in non‐small‐cell lung cancer
title METTL3‐mediated m6A mRNA contributes to the resistance of carbon‐ion radiotherapy in non‐small‐cell lung cancer
title_full METTL3‐mediated m6A mRNA contributes to the resistance of carbon‐ion radiotherapy in non‐small‐cell lung cancer
title_fullStr METTL3‐mediated m6A mRNA contributes to the resistance of carbon‐ion radiotherapy in non‐small‐cell lung cancer
title_full_unstemmed METTL3‐mediated m6A mRNA contributes to the resistance of carbon‐ion radiotherapy in non‐small‐cell lung cancer
title_short METTL3‐mediated m6A mRNA contributes to the resistance of carbon‐ion radiotherapy in non‐small‐cell lung cancer
title_sort mettl3‐mediated m6a mrna contributes to the resistance of carbon‐ion radiotherapy in non‐small‐cell lung cancer
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9807515/
https://www.ncbi.nlm.nih.gov/pubmed/36114749
http://dx.doi.org/10.1111/cas.15590
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