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Review
. 2025 Apr 17:16:1534655.
doi: 10.3389/fphar.2025.1534655. eCollection 2025.

Methyltransferase-like 3 is a target for the diagnose and therapy of clear cell renal carcinoma

Dongqiong Xiao  1 , Xiaojuan Su  1
Affiliations
Review

Methyltransferase-like 3 is a target for the diagnose and therapy of clear cell renal carcinoma

Dongqiong Xiao et al. Front Pharmacol. .

Abstract

Patients diagnosed with clear cell renal carcinoma (ccRCC) frequently exhibit metastatic disease, which complicates treatment strategies, underscoring the urgent need for mechanistic insights and early diagnostic biomarkers. Current research is dedicated to uncovering the mechanisms behind ccRCC development and resistance to treatment, with a particular focus on the role of methyltransferase-like 3 (METTL3) in RNA N6-methyladenosine modification, a key gene regulatory process. This review synthesizes current evidence on METTL3's functions, revealing its oncogenic activity through m6A-mediated regulation of RNA stability and translation, which promotes tumor progression, metastasis, and chemoresistance. We further explore METTL3's dual diagnostic and therapeutic relevance, including its utility as a prognostic biomarker and its targeting via novel strategies such as small-molecule inhibitors (e.g., Erianin) and combination therapies with mTOR or immune checkpoint inhibitors. By consolidating these advances, this review positions METTL3 as a critical node for advancing precision medicine in ccRCC.

Keywords: clear cell renal carcinoma; diagnosis biomarker; drug resistance; methyltransferase-like 3; pathogenesis; therapeutic target.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Functional Roles of METTL3 in ccRCC. The RNA m6A modification mediated by METTL3 plays a pivotal role in the oncogenesis, epithelial-mesenchymal transition, and advancement of ccRCC by coordinating various cellular mechanisms, such as the modulation of cell cycle progression, lipid metabolic pathways, immune cell infiltration, and evasion, as well as the regulation of glycolytic metabolism. Methyltransferase-like 3 (METTL3). N6-methyladenosine (m6A). Clear cell renal carcinoma (ccRCC).
FIGURE 2
FIGURE 2
Molecular Mechanisms of METTL3 in ccRCC. The molecular mechanisms of METTL3 in ccRCC include different METTL3-RNA axes. Methyltransferase-like 3 (METTL3). N6-methyladenosine (m6A). Clear cell renal carcinoma (ccRCC). ATP-binding cassette subfamily D member 1 (ABCD1). Open reading frame 50 (ORF50). On-SMC condensin I complex subunit H (NCAPH). YTH N6-methyladenosine RNA binding protein (YTHDF). Dihydrolipoamide branched chain transacylase E2 (DBT). Yes1-associated transcriptional regulator (YAP). Nuclear enriched abundant transcript 1 (NEAT1).
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