METTL14, known as Methyltransferase-like 14, is a major RNA N6-adenosine methyltransferase. It forms part of the RNA m6A methyltransferase complex, regulating RNA function through m6A modification, which impacts numerous biological processes like cell differentiation, metabolism, and disease development [1-5].

In colorectal cancer, METTL14 expression is downregulated and is an independent prognostic factor. Its deletion promotes tumor growth in mouse models. It inhibits cell migration, invasion, and metastasis by mediating m6A modification of SOX4 mRNA [1]. In p53-wild-type CRC cells, METTL14 is transcriptionally activated by wild-type p53 and suppresses tumor growth by restraining aerobic glycolysis [2].

In diabetic cardiomyopathy, METTL14 is downregulated in cardiomyocytes. Its overexpression suppresses pyroptosis and DCM by downregulating lncRNA TINCR [3].

In endothelial cells, METTL14 promotes FOXO1 expression through m6A modification, aggravating endothelial inflammation and atherosclerosis. METTL14 knockout mice show reduced atherosclerotic plaque development [4].

In hematopoiesis, silencing METTL14 in normal hematopoietic stem/progenitor cells and AML cells promotes terminal myeloid differentiation and inhibits AML cell survival/proliferation [5].

In summary, METTL14 is crucial in multiple disease-related biological processes. Gene knockout mouse models have been instrumental in revealing its roles in diseases such as colorectal cancer, diabetic cardiomyopathy, atherosclerosis, and in hematopoiesis. These findings enhance our understanding of the underlying disease mechanisms and suggest METTL14 as a potential therapeutic target.