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Review
. 2025 Jun;480(6):3429-3454.
doi: 10.1007/s11010-025-05208-z. Epub 2025 Jan 24.

METTL3: a multifunctional regulator in diseases

Na Li  1 , Xiang Wei  1 , Jian Dai  2 , Jinfeng Yang  3 , Sizheng Xiong  4
Affiliations
Review

METTL3: a multifunctional regulator in diseases

Na Li et al. Mol Cell Biochem. 2025 Jun.

Abstract

N6-methyladenosine (m6A) methylation is the most prevalent and abundant internal modification of mRNAs and is catalyzed by the methyltransferase complex. Methyltransferase-like 3 (METTL3), the best-known m6A methyltransferase, has been confirmed to function as a multifunctional regulator in the reversible epitranscriptome modulation of m6A modification according to follow-up studies. Accumulating evidence in recent years has shown that METTL3 can regulate a variety of functional genes, that aberrant expression of METTL3 is usually associated with many pathological conditions, and that its expression regulatory mechanism is related mainly to its methyltransferase activity or mRNA posttranslational modification. In this review, we discuss the regulatory functions of METTL3 in various diseases, including metabolic diseases, cardiovascular diseases, and cancer. We focus mainly on recent progress in identifying the downstream target genes of METTL3 and its underlying molecular mechanisms and regulators in the above systems. Studies have revealed that the use of METTL3 as a therapeutic target and a new diagnostic biomarker has broad prospects. We hope that this review can serve as a reference for further studies.

Keywords: Cancer; Cardiovascular diseases; Drug therapy; METTL3; Metabolic diseases; m6A.

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Conflict of interest statement

Declarations. Conflicts of Interest: The authors declare no competing interests. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable.

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