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This article reviews the dual regulatory role of METTL14 in tumorigenesis and its underlying mechanisms.

March 7, 2026Open Access

The dual regulatory role of METTL14-mediated m6A modification in tumorigenesis and its underlying mechanisms

Key Points

This article reviews the dual regulatory role of METTL14 in tumorigenesis and its underlying mechanisms.
Systematic review of literature on METTL14's roles in various cancers
Analysis of the dual effects of METTL14 on tumor progression
Examined mechanisms of METTL14 in regulating non-coding RNAs and immune responses
METTL14 primarily suppresses tumors in hepatocellular and colorectal cancers
In pancreatic and nasopharyngeal cancers, METTL14 promotes malignancy
Identified its role in shaping the tumor microenvironment and regulating immune checkpoints

Abstract

N 6 -methyladenosine (m 6 A), as the most abundant RNA epitranscriptional modification in eukaryotes, its key component of the methyltransferase complex, METTL14, not only cooperates in catalyzing m 6 A deposition but also has functions independent of methyltransferase activity. This article systematically reviews the dual regulatory role of METTL14 in tumors and its molecular mechanisms, mainly organizing the relevant research in a logical sequence of “tumor suppressive effect - tumor promoting effect - controversial or context-dependent”. Studies have shown that METTL14 often plays a tumor suppressive role in tumors such as hepatocellular carcinoma and colorectal cancer, while in pancreatic cancer and nasopharyngeal carcinoma, it mostly promotes malignant progression, showing a high degree of context dependence. This article focuses on two key mechanisms: on the one hand, METTL14 precisely regulates the processing, stability, and function of non-coding RNAs (including miRNAs, lncRNAs, and circRNAs) through m 6 A modification, reshaping the competitive endogenous RNA (ceRNA) network; on the other hand, it shapes an immunosuppressive tumor microenvironment by directly upregulating immune checkpoints such as PD-L1, mediating metabolism-immune interactions, and regulating the function of immune cells. Its functional duality also stems from the selective regulation of key pathways such as PI3K/AKT, as well as the differential interpretation by different m 6 A readers (such as YTHDF2 and IGF2BPs). Given the close association of these mechanisms with clinical prognosis, the expression level of METTL14 shows significant potential as a prognostic marker and therapeutic target; in the future, it is necessary to combine single-cell multi-omics and other technologies to analyze its dynamic regulatory network in specific tumor contexts and explore precise treatment strategies based on synthetic lethality or targeting downstream effector molecules.

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