Methyltransferase-like Proteins in Cancer Biology and Potential Therapeutic Targeting
Overview
Oncology
Affiliations
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.
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.
Liu Z, Ling Z Heliyon. 2025; 11(2):e41724.
PMID: 39906812 PMC: 11791267. DOI: 10.1016/j.heliyon.2025.e41724.