N6-methyladenosine Methylation in Ophthalmic Diseases: From Mechanisms to Potential Applications

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 Jan 9

PMID 38192819

Authors

Bingyan Li

Zicong Wang

Haixiang Zhou

Jingling Zou

Shigeo Yoshida

Yedi Zhou

Affiliations

Soon will be listed here.

Abstract

N6-methyladenosine (mA) modification, as the most common modification method in eukaryotes, is widely involved in numerous physiological and pathological processes, such as embryonic development, malignancy, immune regulation, and premature aging. Under pathological conditions of ocular diseases, changes in mA modification and its metabolism can be detected in aqueous and vitreous humor. At the same time, an increasing number of studies showed that mA modification is involved in the normal development of eye structures and the occurrence and progress of many ophthalmic diseases, especially ocular neovascular diseases, such as diabetic retinopathy, age-related macular degeneration, and melanoma. In this review, we summarized the latest progress regarding mA modification in ophthalmic diseases, changes in mA modification-related enzymes in various pathological states and their upstream and downstream regulatory networks, provided new prospects for mA modification in ophthalmic diseases and new ideas for clinical diagnosis and treatment.

Citing Articles

Mettl3-Mediated N6-Methyladenosine Modification Mitigates Ganglion Cell Loss and Retinal Dysfunction in Retinal Ischemia-Reperfusion Injury by Inhibiting FoxO1-Mediated Autophagy.

Zhu F, Feng J, Pan Y, Ouyang L, He T, Xing Y Invest Ophthalmol Vis Sci. 2025; 66(2):58.

PMID: 39982709 PMC: 11855173. DOI: 10.1167/iovs.66.2.58.

References

Jamal A, Dalhat M, Jahan S, Choudhry H, Imran Khan M . BTYNB, an inhibitor of RNA binding protein IGF2BP1 reduces proliferation and induces differentiation of leukemic cancer cells. Saudi J Biol Sci. 2023; 30(3):103569. PMC: 9932463. DOI: 10.1016/j.sjbs.2023.103569. View

Tang H, Huang L, Hu J . Inhibition of the m6A Methyltransferase METTL3 Attenuates the Inflammatory Response in Fusarium solani-Induced Keratitis via the NF-κB Signaling Pathway. Invest Ophthalmol Vis Sci. 2022; 63(11):2. PMC: 9547362. DOI: 10.1167/iovs.63.11.2. View

Elia G, Fallahi P, Ragusa F, Paparo S, Mazzi V, Benvenga S . Precision Medicine in Graves' Disease and Ophthalmopathy. Front Pharmacol. 2021; 12:754386. PMC: 8581657. DOI: 10.3389/fphar.2021.754386. View

Meng J, Liu X, Tang S, Liu Y, Zhao C, Zhou Q . METTL3 inhibits inflammation of retinal pigment epithelium cells by regulating NR2F1 in an mA-dependent manner. Front Immunol. 2022; 13:905211. PMC: 9351451. DOI: 10.3389/fimmu.2022.905211. View

Yu J, Chai P, Xie M, Ge S, Ruan J, Fan X . Histone lactylation drives oncogenesis by facilitating mA reader protein YTHDF2 expression in ocular melanoma. Genome Biol. 2021; 22(1):85. PMC: 7962360. DOI: 10.1186/s13059-021-02308-z. View

Zhang W, Wu T, Zhang Y, Kang W, Du C, You Q . Targeting mA binding protein YTHDFs for cancer therapy. Bioorg Med Chem. 2023; 90:117373. DOI: 10.1016/j.bmc.2023.117373. View

Huang L, Tang H, Hu J . METTL3 Attenuates Inflammation in Fusarium solani-Induced Keratitis via the PI3K/AKT Signaling Pathway. Invest Ophthalmol Vis Sci. 2022; 63(10):20. PMC: 9526359. DOI: 10.1167/iovs.63.10.20. View

Nombela P, Miguel-Lopez B, Blanco S . The role of mA, mC and Ψ RNA modifications in cancer: Novel therapeutic opportunities. Mol Cancer. 2021; 20(1):18. PMC: 7812662. DOI: 10.1186/s12943-020-01263-w. View

Xu C, Liu K, Tempel W, Demetriades M, Aik W, Schofield C . Structures of human ALKBH5 demethylase reveal a unique binding mode for specific single-stranded N6-methyladenosine RNA demethylation. J Biol Chem. 2014; 289(25):17299-311. PMC: 4067165. DOI: 10.1074/jbc.M114.550350. View

10.

Hao L, Yin J, Yang H, Li C, Zhu L, Liu L . ALKBH5-mediated mA demethylation of FOXM1 mRNA promotes progression of uveal melanoma. Aging (Albany NY). 2021; 13(3):4045-4062. PMC: 7906204. DOI: 10.18632/aging.202371. View

11.

Wang Y, Wu Z, Huang Y, Zhang Y . Hsa_circ_0004058 inhibits apoptosis of SRA01/04 cells by promoting autophagy via miR-186/ATG7 axis. Exp Eye Res. 2021; 211:108721. DOI: 10.1016/j.exer.2021.108721. View

12.

Huang L, Liang H, Wang S, Chen S . mA writer complex promotes timely differentiation and survival of retinal progenitor cells in zebrafish. Biochem Biophys Res Commun. 2021; 567:171-176. DOI: 10.1016/j.bbrc.2021.06.043. View

13.

Xin Y, He Q, Liang H, Zhang K, Guo J, Zhong Q . mA epitranscriptomic modification regulates neural progenitor-to-glial cell transition in the retina. Elife. 2022; 11. PMC: 9718531. DOI: 10.7554/eLife.79994. View

14.

Huang W, Chen T, Fang K, Zeng Z, Ye H, Chen Y . N6-methyladenosine methyltransferases: functions, regulation, and clinical potential. J Hematol Oncol. 2021; 14(1):117. PMC: 8313886. DOI: 10.1186/s13045-021-01129-8. View

15.

Liao L, He Y, Li S, Zhang G, Yu W, Yang J . Anti-HIV Drug Elvitegravir Suppresses Cancer Metastasis via Increased Proteasomal Degradation of m6A Methyltransferase METTL3. Cancer Res. 2022; 82(13):2444-2457. DOI: 10.1158/0008-5472.CAN-21-4124. View

16.

Shan K, Zhou R, Xiang J, Sun Y, Liu C, Lv M . FTO regulates ocular angiogenesis via mA-YTHDF2-dependent mechanism. Exp Eye Res. 2020; 197:108107. DOI: 10.1016/j.exer.2020.108107. View

17.

Chen W, Qi J, Hang Y, Wu J, Zhou X, Chen J . Simvastatin is beneficial to lung cancer progression by inducing METTL3-induced m6A modification on EZH2 mRNA. Eur Rev Med Pharmacol Sci. 2020; 24(8):4263-4270. DOI: 10.26355/eurrev_202004_21006. View

18.

Liao J, Wei Y, Liang J, Wen J, Chen X, Zhang B . Insight into the structure, physiological function, and role in cancer of m6A readers-YTH domain-containing proteins. Cell Death Discov. 2022; 8(1):137. PMC: 8964710. DOI: 10.1038/s41420-022-00947-0. View

19.

Shi Y, Wang X, Wang J, Wang X, Zhou H, Zhang L . The dual roles of A20 in cancer. Cancer Lett. 2021; 511:26-35. DOI: 10.1016/j.canlet.2021.04.017. View

20.

Wang Y, Li J, Han X, Wang N, Song C, Wang R . Identification of Clausine E as an inhibitor of fat mass and obesity-associated protein (FTO) demethylase activity. J Mol Recognit. 2019; 32(10):e2800. DOI: 10.1002/jmr.2800. View