M6A RNA modification: focusing on non-small cell lung cancer progression, therapeutic strategies and challenges

N6-methyladenosine (m6A) modification is a pivotal mechanism in RNA epigenetics, with profound implications for lung cancer (LC) biology. This review synthesizes current knowledge on m6A’s multifaceted regulatory networks in non-small cell lung cancer (NSCLC), elucidating its roles in tumor prolifer...

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Main Authors: Yuyang Yan, Jiarui Yin, Quan Ding, Yan Lu, Shuhua Gou, Xi Xu, Yulin Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1622359/full
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author Yuyang Yan
Jiarui Yin
Quan Ding
Yan Lu
Shuhua Gou
Xi Xu
Yulin Li
author_facet Yuyang Yan
Jiarui Yin
Quan Ding
Yan Lu
Shuhua Gou
Xi Xu
Yulin Li
author_sort Yuyang Yan
collection DOAJ
description N6-methyladenosine (m6A) modification is a pivotal mechanism in RNA epigenetics, with profound implications for lung cancer (LC) biology. This review synthesizes current knowledge on m6A’s multifaceted regulatory networks in non-small cell lung cancer (NSCLC), elucidating its roles in tumor proliferation, apoptosis, invasion, and metastasis. We further explore how m6A governs metabolic reprogramming—including glycolysis and ferroptosis—angiogenesis, and tumor microenvironment (TME) remodeling. Additionally, m6A-mediated modification of non-coding RNAs contributes to LC malignancy, underscoring its potential as a diagnostic and prognostic biomarker. These findings also offer novel strategies to overcome therapeutic resistance, a critical challenge in NSCLC treatment. Despite its promise, clinical translation of m6A-targeted interventions faces hurdles, such as the lack of standardized detection methods, the complexity of m6A-associated regulatory networks, and unresolved crosstalk with other RNA modifications. Future research should prioritize multi-omics approaches to resolve these challenges and advance m6A from mechanistic discovery toward clinical application. By addressing these gaps, m6A modulation may emerge as a transformative avenue in precision oncology.
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publisher Frontiers Media S.A.
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series Frontiers in Oncology
spelling doaj-art-68bd2bc2caa94cf48a2ac82039296ad32025-08-20T03:50:49ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-07-011510.3389/fonc.2025.16223591622359M6A RNA modification: focusing on non-small cell lung cancer progression, therapeutic strategies and challengesYuyang YanJiarui YinQuan DingYan LuShuhua GouXi XuYulin LiN6-methyladenosine (m6A) modification is a pivotal mechanism in RNA epigenetics, with profound implications for lung cancer (LC) biology. This review synthesizes current knowledge on m6A’s multifaceted regulatory networks in non-small cell lung cancer (NSCLC), elucidating its roles in tumor proliferation, apoptosis, invasion, and metastasis. We further explore how m6A governs metabolic reprogramming—including glycolysis and ferroptosis—angiogenesis, and tumor microenvironment (TME) remodeling. Additionally, m6A-mediated modification of non-coding RNAs contributes to LC malignancy, underscoring its potential as a diagnostic and prognostic biomarker. These findings also offer novel strategies to overcome therapeutic resistance, a critical challenge in NSCLC treatment. Despite its promise, clinical translation of m6A-targeted interventions faces hurdles, such as the lack of standardized detection methods, the complexity of m6A-associated regulatory networks, and unresolved crosstalk with other RNA modifications. Future research should prioritize multi-omics approaches to resolve these challenges and advance m6A from mechanistic discovery toward clinical application. By addressing these gaps, m6A modulation may emerge as a transformative avenue in precision oncology.https://www.frontiersin.org/articles/10.3389/fonc.2025.1622359/fullM6Anon-small cell lung cancertherapeutic strategiesmetabolic reprogrammingRNA epigenetic regulation
spellingShingle Yuyang Yan
Jiarui Yin
Quan Ding
Yan Lu
Shuhua Gou
Xi Xu
Yulin Li
M6A RNA modification: focusing on non-small cell lung cancer progression, therapeutic strategies and challenges
Frontiers in Oncology
M6A
non-small cell lung cancer
therapeutic strategies
metabolic reprogramming
RNA epigenetic regulation
title M6A RNA modification: focusing on non-small cell lung cancer progression, therapeutic strategies and challenges
title_full M6A RNA modification: focusing on non-small cell lung cancer progression, therapeutic strategies and challenges
title_fullStr M6A RNA modification: focusing on non-small cell lung cancer progression, therapeutic strategies and challenges
title_full_unstemmed M6A RNA modification: focusing on non-small cell lung cancer progression, therapeutic strategies and challenges
title_short M6A RNA modification: focusing on non-small cell lung cancer progression, therapeutic strategies and challenges
title_sort m6a rna modification focusing on non small cell lung cancer progression therapeutic strategies and challenges
topic M6A
non-small cell lung cancer
therapeutic strategies
metabolic reprogramming
RNA epigenetic regulation
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1622359/full
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