» Articles » PMID: 37533128

Methyltransferase-like Proteins in Cancer Biology and Potential Therapeutic Targeting

Overview
Journal J Hematol Oncol
Publisher Biomed Central
Specialties Hematology
Oncology
Date 2023 Aug 2
PMID 37533128
Authors
Affiliations
Soon will be listed here.
Abstract

RNA modification has recently become a significant process of gene regulation, and the methyltransferase-like (METTL) family of proteins plays a critical role in RNA modification, methylating various types of RNAs, including mRNA, tRNA, microRNA, rRNA, and mitochondrial RNAs. METTL proteins consist of a unique seven-beta-strand domain, which binds to the methyl donor SAM to catalyze methyl transfer. The most typical family member METTL3/METTL14 forms a methyltransferase complex involved in N6-methyladenosine (m6A) modification of RNA, regulating tumor proliferation, metastasis and invasion, immunotherapy resistance, and metabolic reprogramming of tumor cells. METTL1, METTL4, METTL5, and METTL16 have also been recently identified to have some regulatory ability in tumorigenesis, and the rest of the METTL family members rely on their methyltransferase activity for methylation of different nucleotides, proteins, and small molecules, which regulate translation and affect processes such as cell differentiation and development. Herein, we summarize the literature on METTLs in the last three years to elucidate their roles in human cancers and provide a theoretical basis for their future use as potential therapeutic targets.

Citing Articles

RNA Modification in Metabolism.

Liu Y, Sun Z, Gui D, Zhao Y, Xu Y MedComm (2020). 2025; 6(3):e70135.

PMID: 40066222 PMC: 11892166. DOI: 10.1002/mco2.70135.


The Role of MATN3 in Cancer Prognosis and Immune Infiltration Across Multiple Tumor Types.

Qin C, Qin H, Xie H, Li Y, Bi A, Liao X J Cancer. 2025; 16(5):1519-1537.

PMID: 39991588 PMC: 11843250. DOI: 10.7150/jca.103523.


The m6A revolution: transforming tumor immunity and enhancing immunotherapy outcomes.

Shi T, Zhang H, Chen Y Cell Biosci. 2025; 15(1):27.

PMID: 39987091 PMC: 11846233. DOI: 10.1186/s13578-025-01368-z.


Exploring m6A modifications in gastric cancer: from molecular mechanisms to clinical applications.

Li P, Fang X, Huang D Eur J Med Res. 2025; 30(1):98.

PMID: 39940056 PMC: 11823136. DOI: 10.1186/s40001-025-02353-5.


Golgi scaffold protein PAQR11 in pan-cancer landscape: A comprehensive bioinformatics exploration of expression patterns, prognostic significance, and potential immunological function.

Liu Z, Ling Z Heliyon. 2025; 11(2):e41724.

PMID: 39906812 PMC: 11791267. DOI: 10.1016/j.heliyon.2025.e41724.


References
1.
Zhu S, Wu Y, Zhang X, Peng S, Xiao H, Chen S . Targeting N-methylguanosine tRNA modification blocks hepatocellular carcinoma metastasis after insufficient radiofrequency ablation. Mol Ther. 2022; 31(6):1596-1614. PMC: 10278047. DOI: 10.1016/j.ymthe.2022.08.004. View

2.
Liu P, Fan B, Othmane B, Hu J, Li H, Cui Y . mA-induced lncDBET promotes the malignant progression of bladder cancer through FABP5-mediated lipid metabolism. Theranostics. 2022; 12(14):6291-6307. PMC: 9475447. DOI: 10.7150/thno.71456. View

3.
Liu Q, Li Z, He L, Li K, Hu C, Chen J . Molecular Characterization and Clinical Relevance of N-Methyladenosine Regulators in Metastatic Prostate Cancer. Front Oncol. 2022; 12:914692. PMC: 9257042. DOI: 10.3389/fonc.2022.914692. View

4.
Ruszkowska A, Ruszkowski M, Dauter Z, Brown J . Structural insights into the RNA methyltransferase domain of METTL16. Sci Rep. 2018; 8(1):5311. PMC: 5871880. DOI: 10.1038/s41598-018-23608-8. View

5.
Yu R, Wei Y, He C, Zhou P, Yang H, Deng C . Integrative Analyses of m6A Regulators Identify that METTL3 is Associated with HPV Status and Immunosuppressive Microenvironment in HPV-related Cancers. Int J Biol Sci. 2022; 18(9):3874-3887. PMC: 9254478. DOI: 10.7150/ijbs.70674. View