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N(6)-methyladenosine (m(6)A) methyltransferase KIAA1429 accelerates the gefitinib resistance of non-small-cell lung cancer

N(6)-methyladenosine (m(6)A) modification has been convincingly identified to be a critical regulator in human cancer. However, the contribution of m(6)A to NSCLC gefitinib resistance is still largely unknown. Here, we screened and identified that m(6)A methyltransferase KIAA1429 was highly expresse...

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Autores principales: Tang, Jun, Han, Tianci, Tong, Wei, Zhao, Jian, Wang, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128911/
https://www.ncbi.nlm.nih.gov/pubmed/34001850
http://dx.doi.org/10.1038/s41420-021-00488-y
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author Tang, Jun
Han, Tianci
Tong, Wei
Zhao, Jian
Wang, Wei
author_facet Tang, Jun
Han, Tianci
Tong, Wei
Zhao, Jian
Wang, Wei
author_sort Tang, Jun
collection PubMed
description N(6)-methyladenosine (m(6)A) modification has been convincingly identified to be a critical regulator in human cancer. However, the contribution of m(6)A to NSCLC gefitinib resistance is still largely unknown. Here, we screened and identified that m(6)A methyltransferase KIAA1429 was highly expressed in gefitinib-resistant NSCLC cells (PC9-GR), tissues, and closely related to unfavorable survival. Functionally, KIAA1429 accelerated the gefitinib resistance of NSCLC in vitro. Depletion of KIAA1429 repressed the tumor growth of PC9-GR cells in vivo. Mechanistically, KIAA1429 enhanced the mRNA stability of HOXA1 through targeting its 3′-untranslated regions (3′-UTR). Overall, our findings indicate that KIAA1429 plays essential oncogenic roles in NSCLC gefitinib resistance, which may provide a feasible therapeutic target for NSCLC.
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spelling pubmed-81289112021-05-27 N(6)-methyladenosine (m(6)A) methyltransferase KIAA1429 accelerates the gefitinib resistance of non-small-cell lung cancer Tang, Jun Han, Tianci Tong, Wei Zhao, Jian Wang, Wei Cell Death Discov Article N(6)-methyladenosine (m(6)A) modification has been convincingly identified to be a critical regulator in human cancer. However, the contribution of m(6)A to NSCLC gefitinib resistance is still largely unknown. Here, we screened and identified that m(6)A methyltransferase KIAA1429 was highly expressed in gefitinib-resistant NSCLC cells (PC9-GR), tissues, and closely related to unfavorable survival. Functionally, KIAA1429 accelerated the gefitinib resistance of NSCLC in vitro. Depletion of KIAA1429 repressed the tumor growth of PC9-GR cells in vivo. Mechanistically, KIAA1429 enhanced the mRNA stability of HOXA1 through targeting its 3′-untranslated regions (3′-UTR). Overall, our findings indicate that KIAA1429 plays essential oncogenic roles in NSCLC gefitinib resistance, which may provide a feasible therapeutic target for NSCLC. Nature Publishing Group UK 2021-05-17 /pmc/articles/PMC8128911/ /pubmed/34001850 http://dx.doi.org/10.1038/s41420-021-00488-y Text en © The Author(s) 2021 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 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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Tang, Jun
Han, Tianci
Tong, Wei
Zhao, Jian
Wang, Wei
N(6)-methyladenosine (m(6)A) methyltransferase KIAA1429 accelerates the gefitinib resistance of non-small-cell lung cancer
title N(6)-methyladenosine (m(6)A) methyltransferase KIAA1429 accelerates the gefitinib resistance of non-small-cell lung cancer
title_full N(6)-methyladenosine (m(6)A) methyltransferase KIAA1429 accelerates the gefitinib resistance of non-small-cell lung cancer
title_fullStr N(6)-methyladenosine (m(6)A) methyltransferase KIAA1429 accelerates the gefitinib resistance of non-small-cell lung cancer
title_full_unstemmed N(6)-methyladenosine (m(6)A) methyltransferase KIAA1429 accelerates the gefitinib resistance of non-small-cell lung cancer
title_short N(6)-methyladenosine (m(6)A) methyltransferase KIAA1429 accelerates the gefitinib resistance of non-small-cell lung cancer
title_sort n(6)-methyladenosine (m(6)a) methyltransferase kiaa1429 accelerates the gefitinib resistance of non-small-cell lung cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128911/
https://www.ncbi.nlm.nih.gov/pubmed/34001850
http://dx.doi.org/10.1038/s41420-021-00488-y
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