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

## TL;DR

This paper explores how METTL14, a key RNA modifier, can both suppress and promote tumors depending on the cancer type and its underlying mechanisms.

## Contribution

The paper systematically reviews the dual regulatory role of METTL14 in tumorigenesis and its molecular mechanisms.

## Key findings

- METTL14 acts as a tumor suppressor in hepatocellular and colorectal cancers but promotes malignancy in pancreatic and nasopharyngeal cancers.
- METTL14 regulates non-coding RNAs and immune checkpoints, influencing tumor progression and the tumor microenvironment.
- The dual function of METTL14 is linked to pathways like PI3K/AKT and m6A readers such as YTHDF2 and IGF2BPs.

## Abstract

N6-methyladenosine (m6A), as the most abundant RNA epitranscriptional modification in eukaryotes, its key component of the methyltransferase complex, METTL14, not only cooperates in catalyzing m6A 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 m6A 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 m6A 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.