METTL1, the methyltransferase-like 1, is a key component of the tRNA N7-methylguanosine (m7G) methyltransferase complex along with WDR4. It catalyzes m7G modification of tRNAs, which is crucial for tRNA stability and function, and is involved in processes like mRNA translation [5,7,9]. This modification impacts various biological processes and is associated with multiple diseases, especially cancers [1,2,3,4,6,7,8].

Depletion of METTL1 in cancer cells leads to decreased abundance of m7G-modified tRNAs, altered cell cycle, and inhibited oncogenicity. For example, in hepatocellular carcinoma (HCC), METTL1 knockdown overrode lenvatinib resistance by impairing cell proliferation and promoting apoptosis. In bladder cancer, silencing METTL1 suppressed cell proliferation, migration, and invasion both in vitro and in vivo. In prostate cancer, METTL1 depletion increased intratumoural infiltration of pro-inflammatory immune cells [1,2,3,8]. In post-radiofrequency ablation recurrent HCC, heat-mediated METTL1 upregulation enhanced TGF-β2 translation to form an immunosuppressive environment. Interrupting the METTL1-TGF-β2-PMN-MDSC axis could prevent HCC recurrence [4].

In conclusion, METTL1-mediated m7G tRNA modification is essential in regulating various biological processes. Through gene knockout or knockdown studies in different cancer models, it has been shown to play a significant role in cancer development, drug resistance, and immunosuppression. Understanding METTL1-related mechanisms provides potential therapeutic targets for cancer treatment.