Research progress on the role of m6A methylation modification in lung adenocarcinoma_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

WANG Junbin ^1,2 , QIANG Guangliang ³ , TANG Jizheng ³ ,  ZHANG Zhe ¹

1. Department of Cardiac Surgery, Peking University Third Hospital, Beijing, 100191, P. R. China;
2. Department of Thoracic Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, Guangdong, P. R. China;
3. Department of Thoracic Surgery, Peking University Third Hospital , Beijing, 100191, P. R. China;

Corresponding?author：

ZHANG Zhe, Email: zhangzhe@bjmu.edu.cn

Keywords：

lncRNA; lung adenocarcinoma; m6A; tumour progression; biomarkers; review

DOI：

10.7507/1007-4848.202509078

Video：

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[Abstract]The pathogenesis of lung adenocarcinoma (LUAD) is closely associated with the aberrant expression of long non-coding RNAs (lncRNAs), whose functions are precisely regulated by the important post-transcriptional modification N6-methyladenosine (m6A). Recent studies have revealed that m6A modification plays a critical role in malignant phenotypes of LUAD, including proliferation, invasion, metastasis, and drug resistance, by influencing the stability, processing, and function of lncRNAs. This review systematically summarizes recent advances in understanding the role of m6A-modified lncRNAs in LUAD, with a focus on the functional mechanisms of the m6A-lncRNA regulatory network in tumor progression. It also discusses their clinical potential as novel biomarkers and therapeutic targets, aiming to provide new theoretical insights for the precise diagnosis and treatment of LUAD.

1.	Smolarz B, ?ukasiewicz H, Samulak D, et al. Lung cancer-epidemiology, pathogenesis, treatment and molecular aspect (review of literature). Int J Mol Sci, 2025, 26(5): 2049.
2.	Kim SY, Park HS, Chiang AC. Small cell lung cancer: a review. JAMA, 2025, 333(21): 1906-1917.
3.	Yang C, Huang H, Li Y, et al. lncRNA PCAT6 promotes proliferation, migration, invasion, and epithelial-mesenchymal transition of lung adenocarcinoma cell by targeting miR-545-3p. Mol Biol Rep, 2023, 50(4): 3557-3568.
4.	Ding Q, Chen D, Wang W, et al. Progress in research on the cribriform component in lung adenocarcinoma. Chin J Lung Cancer, 2020, 23(7): 621-625.
5.	Wei H, Zhang S, Lin X, et al. Differential expression and clinical significance of long non-coding RNAs in the development and progression of lung adenocarcinoma. Front Oncol, 2024, 14: 1411672.
6.	Dai C, He Q, Fu R, et al. Epigenetic and epitranscriptomic role of lncRNA in carcinogenesis (review). Int J Oncol, 2025, 66(4): 29.
7.	Thangavelu L, Goyal A, Afzal M, et al. Pyroptosis in lung cancer: the emerging role of non-coding RNAs. Pathol Res Pract, 2024, 263: 155619.
8.	Dang HX, White NM, Rozycki EB, et al. Long non-coding RNA LCAL62 / LINC00261 is associated with lung adenocarcinoma prognosis. Heliyon, 2020, 6(3): e03521.
9.	Jiang F, Huang X, Ling L, et al. Long noncoding RNA ZBED5-AS1 facilitates tumor progression and metastasis in lung adenocarcinoma via ZNF146/ATR/Chk1 axis. Int J Mol Sci, 2023, 24(18): 13925.
10.	Guo H, Feng Y, Yu H, et al. A novel lncRNA, loc107985872, promotes lung adenocarcinoma progression via the Notch1 signaling pathway with exposure to traffic-originated PM2.5 organic extract. Environ Pollut, 2020, 266(Pt 1): 115307.
11.	Chen Y, Wang J, Gu L, et al. lncRNA NR_146969 promotes the progression of lung adenocarcinoma. Exp Cell Res, 2025, 447(2): 114535.
12.	Chen Z, Hu Z, Sui Q, et al. lncRNA FAM83A-AS1 facilitates tumor proliferation and the migration via the HIF-1α/glycolysis axis in lung adenocarcinoma. Int J Biol Sci, 2022, 18(2): 522-535.
13.	Zhang H, Cai W, Miao Y, et al. Long non-coding RNA LINC01116 promotes the proliferation of lung adenocarcinoma by targeting miR-9-5p/CCNE1 axis. J Cell Mol Med, 2024, 28(23): e70270.
14.	Elsakka EGE, Midan HM, Abulsoud AI, et al. Emerging insights: miRNA modulation of ferroptosis pathways in lung cancer. Exp Cell Res, 2024, 442(2): 114272.
15.	Qian Y, Zhang Y, Ji H, et al. LINC01089 suppresses lung adenocarcinoma cell proliferation and migration via miR-301b-3p/STARD13 axis. BMC Pulm Med, 2021, 21(1): 242.
16.	Xiong X, Zhang L, Zang B, et al. High-risk pathological subtype associated FAM83A-AS1 promotes malignancy and glycolysis of lung adenocarcinoma via miR-202-3p/HK2 axis. Oncol Rep, 2023, 49(5): 95.
17.	Cusenza VY, Tameni A, Neri A, et al. The lncRNA epigenetics: the significance of m6A and m5C lncRNA modifications in cancer. Front Oncol, 2023, 13: 1063636.
18.	Khan RIN, Malla WA. m6A modification of RNA and its role in cancer, with a special focus on lung cancer. Genomics, 2021, 113(4): 2860-2869.
19.	Yin X, Zhao S, Zhang M, et al. m6A-modified RIPK4 facilitates proliferation and cisplatin resistance in epithelial ovarian cancer. Gynecol Oncol, 2024, 180: 99-110.
20.	Kang N, Zhao Z, Wang Z, et al. METTL3 regulates thyroid cancer differentiation and chemosensitivity by modulating PAX8. Int J Biol Sci, 2024, 20(9): 3426-3441.
21.	Xu Q, Ren N, Ren L, et al. RNA m6A methylation regulators in liver cancer. Cancer Cell Int, 2024, 24(1): 1.
22.	Ge L, Zhang N, Chen Z, et al. Level of N6-methyladenosine in peripheral blood RNA: a novel predictive biomarker for gastric cancer. Clin Chem, 2020, 66(2): 342-351.
23.	Yang Z, Ma J, Han S, et al. ZFAS1 exerts an oncogenic role via suppressing miR-647 in an m6A-dependent manner in cervical cancer. Onco Targets Ther, 2020, 13: 11795-11806.
24.	Hu N, Ji H. N6-methyladenosine (m6A)-mediated up-regulation of long noncoding RNA LINC01320 promotes the proliferation, migration, and invasion of gastric cancer via miR495-5p/RAB19 axis. Bioengineered, 2021, 12(1): 4081-4091.
25.	Luo XJ, Lu YX, Wang Y, et al. m6A-modified lncRNA FAM83H-AS1 promotes colorectal cancer progression through PTBP1. Cancer Lett, 2024, 598: 217085.
26.	Xu J, Liu C, Qu K, et al. m6A methyltransferase METTL14-mediated RP1-228H13. 5 promotes the occurrence of liver cancer by targeting hsa-miR-205/ZIK1. Oncol Rep, 2024, 51(4): 59.
27.	Wang S, Gu X, Xu D, et al. Comprehensive analysis of m6A modification patterns and m6A-related lncRNAs as potential biomarkers in lung adenocarcinoma. Environ Toxicol, 2024, 39(4): 2285-2303.
28.	Ma C, Gu Z, Yang Y. Development of m6A/m5C/m1A regulated lncRNA signature for prognostic prediction, personalized immune intervention and drug selection in LUAD. J Cell Mol Med, 2024, 28(8): e18282.
29.	Xu D, Wang Z, Li F. KIAA1429 induces m6A modification of LINC01106 to enhance the malignancy of lung adenocarcinoma cells via the JAK/STAT3 pathway. Crit Rev Immunol, 2024, 44(6): 49-61.
30.	Zhang H, Wang SQ, Wang L, et al. m6A methyltransferase METTL3-induced lncRNA SNHG17 promotes lung adenocarcinoma gefitinib resistance by epigenetically repressing LATS2 expression. Cell Death Dis, 2022, 13(7): 657.
31.	Zhang X, Wang DJ, Jia L, et al. N6-methyladenosine-mediated LINC01087 promotes lung adenocarcinoma progression by regulating miR-514a-3p to upregulate centrosome protein 55. Kaohsiung J Med Sci, 2024, 40(9): 801-818.
32.	Huang L, Liu X, Chen Q, et al. TGF-β-induced lncRNA TBUR1 promotes EMT and metastasis in lung adenocarcinoma via hnRNPC-mediated GRB2 mRNA stabilization. Cancer Lett, 2024, 600: 217153.
33.	Wu Z, Zhao Y, Peng Y, et al. lncRNA TMEM99 complexes with IGF2BP2 to inhibit autophagy in lung adenocarcinoma. Adv Sci (Weinh), 2025, 12(33): e07871.
34.	Liu C, Ren Q, Deng J, et al. c-MYC/METTL3/LINC01006 positive feedback loop promotes migration, invasion and proliferation of non-small cell lung cancer. Biomed J, 2024, 47(4): 100664.

1. Smolarz B, ?ukasiewicz H, Samulak D, et al. Lung cancer-epidemiology, pathogenesis, treatment and molecular aspect (review of literature). Int J Mol Sci, 2025, 26(5): 2049.
2. Kim SY, Park HS, Chiang AC. Small cell lung cancer: a review. JAMA, 2025, 333(21): 1906-1917.
3. Yang C, Huang H, Li Y, et al. lncRNA PCAT6 promotes proliferation, migration, invasion, and epithelial-mesenchymal transition of lung adenocarcinoma cell by targeting miR-545-3p. Mol Biol Rep, 2023, 50(4): 3557-3568.
4. Ding Q, Chen D, Wang W, et al. Progress in research on the cribriform component in lung adenocarcinoma. Chin J Lung Cancer, 2020, 23(7): 621-625.
5. Wei H, Zhang S, Lin X, et al. Differential expression and clinical significance of long non-coding RNAs in the development and progression of lung adenocarcinoma. Front Oncol, 2024, 14: 1411672.
6. Dai C, He Q, Fu R, et al. Epigenetic and epitranscriptomic role of lncRNA in carcinogenesis (review). Int J Oncol, 2025, 66(4): 29.
7. Thangavelu L, Goyal A, Afzal M, et al. Pyroptosis in lung cancer: the emerging role of non-coding RNAs. Pathol Res Pract, 2024, 263: 155619.
8. Dang HX, White NM, Rozycki EB, et al. Long non-coding RNA LCAL62 / LINC00261 is associated with lung adenocarcinoma prognosis. Heliyon, 2020, 6(3): e03521.
9. Jiang F, Huang X, Ling L, et al. Long noncoding RNA ZBED5-AS1 facilitates tumor progression and metastasis in lung adenocarcinoma via ZNF146/ATR/Chk1 axis. Int J Mol Sci, 2023, 24(18): 13925.
10. Guo H, Feng Y, Yu H, et al. A novel lncRNA, loc107985872, promotes lung adenocarcinoma progression via the Notch1 signaling pathway with exposure to traffic-originated PM2.5 organic extract. Environ Pollut, 2020, 266(Pt 1): 115307.
11. Chen Y, Wang J, Gu L, et al. lncRNA NR_146969 promotes the progression of lung adenocarcinoma. Exp Cell Res, 2025, 447(2): 114535.
12. Chen Z, Hu Z, Sui Q, et al. lncRNA FAM83A-AS1 facilitates tumor proliferation and the migration via the HIF-1α/glycolysis axis in lung adenocarcinoma. Int J Biol Sci, 2022, 18(2): 522-535.
13. Zhang H, Cai W, Miao Y, et al. Long non-coding RNA LINC01116 promotes the proliferation of lung adenocarcinoma by targeting miR-9-5p/CCNE1 axis. J Cell Mol Med, 2024, 28(23): e70270.
14. Elsakka EGE, Midan HM, Abulsoud AI, et al. Emerging insights: miRNA modulation of ferroptosis pathways in lung cancer. Exp Cell Res, 2024, 442(2): 114272.
15. Qian Y, Zhang Y, Ji H, et al. LINC01089 suppresses lung adenocarcinoma cell proliferation and migration via miR-301b-3p/STARD13 axis. BMC Pulm Med, 2021, 21(1): 242.
16. Xiong X, Zhang L, Zang B, et al. High-risk pathological subtype associated FAM83A-AS1 promotes malignancy and glycolysis of lung adenocarcinoma via miR-202-3p/HK2 axis. Oncol Rep, 2023, 49(5): 95.
17. Cusenza VY, Tameni A, Neri A, et al. The lncRNA epigenetics: the significance of m6A and m5C lncRNA modifications in cancer. Front Oncol, 2023, 13: 1063636.
18. Khan RIN, Malla WA. m6A modification of RNA and its role in cancer, with a special focus on lung cancer. Genomics, 2021, 113(4): 2860-2869.
19. Yin X, Zhao S, Zhang M, et al. m6A-modified RIPK4 facilitates proliferation and cisplatin resistance in epithelial ovarian cancer. Gynecol Oncol, 2024, 180: 99-110.
20. Kang N, Zhao Z, Wang Z, et al. METTL3 regulates thyroid cancer differentiation and chemosensitivity by modulating PAX8. Int J Biol Sci, 2024, 20(9): 3426-3441.
21. Xu Q, Ren N, Ren L, et al. RNA m6A methylation regulators in liver cancer. Cancer Cell Int, 2024, 24(1): 1.
22. Ge L, Zhang N, Chen Z, et al. Level of N6-methyladenosine in peripheral blood RNA: a novel predictive biomarker for gastric cancer. Clin Chem, 2020, 66(2): 342-351.
23. Yang Z, Ma J, Han S, et al. ZFAS1 exerts an oncogenic role via suppressing miR-647 in an m6A-dependent manner in cervical cancer. Onco Targets Ther, 2020, 13: 11795-11806.
24. Hu N, Ji H. N6-methyladenosine (m6A)-mediated up-regulation of long noncoding RNA LINC01320 promotes the proliferation, migration, and invasion of gastric cancer via miR495-5p/RAB19 axis. Bioengineered, 2021, 12(1): 4081-4091.
25. Luo XJ, Lu YX, Wang Y, et al. m6A-modified lncRNA FAM83H-AS1 promotes colorectal cancer progression through PTBP1. Cancer Lett, 2024, 598: 217085.
26. Xu J, Liu C, Qu K, et al. m6A methyltransferase METTL14-mediated RP1-228H13. 5 promotes the occurrence of liver cancer by targeting hsa-miR-205/ZIK1. Oncol Rep, 2024, 51(4): 59.
27. Wang S, Gu X, Xu D, et al. Comprehensive analysis of m6A modification patterns and m6A-related lncRNAs as potential biomarkers in lung adenocarcinoma. Environ Toxicol, 2024, 39(4): 2285-2303.
28. Ma C, Gu Z, Yang Y. Development of m6A/m5C/m1A regulated lncRNA signature for prognostic prediction, personalized immune intervention and drug selection in LUAD. J Cell Mol Med, 2024, 28(8): e18282.
29. Xu D, Wang Z, Li F. KIAA1429 induces m6A modification of LINC01106 to enhance the malignancy of lung adenocarcinoma cells via the JAK/STAT3 pathway. Crit Rev Immunol, 2024, 44(6): 49-61.
30. Zhang H, Wang SQ, Wang L, et al. m6A methyltransferase METTL3-induced lncRNA SNHG17 promotes lung adenocarcinoma gefitinib resistance by epigenetically repressing LATS2 expression. Cell Death Dis, 2022, 13(7): 657.
31. Zhang X, Wang DJ, Jia L, et al. N6-methyladenosine-mediated LINC01087 promotes lung adenocarcinoma progression by regulating miR-514a-3p to upregulate centrosome protein 55. Kaohsiung J Med Sci, 2024, 40(9): 801-818.
32. Huang L, Liu X, Chen Q, et al. TGF-β-induced lncRNA TBUR1 promotes EMT and metastasis in lung adenocarcinoma via hnRNPC-mediated GRB2 mRNA stabilization. Cancer Lett, 2024, 600: 217153.
33. Wu Z, Zhao Y, Peng Y, et al. lncRNA TMEM99 complexes with IGF2BP2 to inhibit autophagy in lung adenocarcinoma. Adv Sci (Weinh), 2025, 12(33): e07871.
34. Liu C, Ren Q, Deng J, et al. c-MYC/METTL3/LINC01006 positive feedback loop promotes migration, invasion and proliferation of non-small cell lung cancer. Biomed J, 2024, 47(4): 100664.

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