N⁶-Methyladenosine (m⁶A) is the most common internal modification of eukaryotic messenger RNA (mRNA) that occurred on the N⁶ nitrogen of adenosine. However, the roles of m⁶A in oral squamous cell carcinoma (OSCC) are still elusive. Here, we investigate the function and mechanism of methyltransferase-like 3 (METTL3) in OSCC tumorigenesis. Clinically, METTL3 was significantly upregulated in tissue samples and correlated with the poor prognosis of OSCC patients. Functionally, loss and gain studies illustrated that METTL3 promoted the proliferation, invasion, and migration of OSCC cells in vitro, and METTL3 knockdown inhibited tumor growth in vivo. Mechanistically, methylated RNA immunoprecipitation sequencing (MeRIP-seq) illustrated that METTL3 targeted the 3′ UTR (near to stop codon) of the c-Myc transcript to install the m⁶A modification, thereby enhancing its stability. Furthermore, results revealed that YTH N⁶-methyladenosine RNA binding protein 1 (YTH domain family, member 1 [YTHDF1]) mediated the m⁶A-increased stability of c-Myc mRNA catalyzed by METTL3. In conclusion, our findings herein identify that METTL3 accelerates the c-Myc stability via YTHDF1-mediated m⁶A modification, thereby giving rise to OSCC tumorigenesis.

N ^6-甲基腺苷（m ⁶ A）是真核信使RNA（mRNA）最常见的内部修饰，发生在腺苷N ⁶氮上。但是，m ⁶ A在口腔鳞状细胞癌（OSCC）中的作用仍然难以捉摸。在此，我们研究了甲基转移酶样3（METTL3）在OSCC肿瘤发生中的功能和机制。临床上，METTL3在组织样品中显着上调，并与OSCC患者的预后不良相关。从功能上，损失和获得研究表明METTL3在体外可促进OSCC细胞的增殖，侵袭和迁移，而METTL3抑制可抑制体内肿瘤的生长。从机理上讲，甲基化的RNA免疫沉淀测序（MeRIP-seq）说明METTL3靶向c-Myc转录本的3'UTR（接近终止密码子）以安装m ⁶ A修饰，从而增强了其稳定性。此外，结果显示YTH N ^6-甲基腺苷RNA结合蛋白1（YTH域家族，成员1 [YTHDF1]）介导了METTL3催化m- ⁶ A增强的c-Myc mRNA的稳定性。总之，本文的发现确定了METTL3通过YTHDF1介导的m ⁶ A修饰来加速c-Myc稳定性，从而引起OSCC肿瘤发生。