METTL13, also known as eEF1A-KNMT and FEAT, is a dual methyltransferase. It targets the N-terminus and Lys55 in eukaryotic translation elongation factor 1 alpha (eEF1A). METTL13-mediated methylation of eEF1A impacts translation dynamics, including the rate of global protein synthesis and translation of specific codons, and is associated with multiple biological processes and diseases, especially cancers [5].

In Ras-driven cancers, METTL13 deletion and eEF1AK55me2 loss significantly reduce neoplastic growth in mouse models and patient-derived xenografts (PDXs) from primary pancreatic and lung tumors, indicating its role in promoting tumorigenesis through increasing translational output [1]. In nasopharyngeal carcinoma (NPC) cells, METTL13 silencing suppresses cellular phenotypes like proliferation, migration, invasion, and angiogenesis in vitro and hinders tumorigenesis in vivo [2]. In gastric cancer, silencing METTL13 suppresses cell proliferation and metastasis in vivo and vitro [4]. In clear cell renal cell carcinoma (ccRCC), knockdown and overexpression of METTL13 respectively lead to an increase and decrease in ccRCC cells' proliferation, viability, migratory and invasive abilities, as well as epithelial-mesenchymal transition (EMT) in vitro, and METTL13 inhibits ccRCC cells' growth and metastasis in vivo [6]. In bladder carcinoma, although the original study was retracted, it was initially reported that METTL13 negatively regulated cell proliferation, migration, and invasion [7,8]. In the heart, cardiomyocyte-specific overexpression of Mettl13 attenuated cardiac contractile dysfunction and fibrosis in response to myocardial infarction in mice, while silencing impaired cardiac function [3].

In conclusion, METTL13 plays a crucial role in multiple biological processes, especially in cancer and cardiac function. Studies using gene knockout or knockdown models in mice and in vitro cell models have revealed its oncogenic or tumor-suppressive roles in different cancers and its protective role in ischemic heart failure, providing potential therapeutic targets for these diseases.