N6-甲基腺苷（m6A）在肿瘤发生和自噬中发挥关键作用。然而，m6A和自噬在口腔鳞状细胞癌（OSCC）恶性进展中的潜在机制尚不清楚。本研究发现，在OSCC中METTL14的表达下调与临床病理特征的进展和不良预后相关。METTL14的沉默显著抑制自噬，在体内促进恶性进展并促进肿瘤生长和转移。我们建立了拉帕霉素诱导的自噬细胞模型，通过RNA测序和甲基化RNA免疫沉淀测序（meRIP-seq）分析，确认了RB1CC1作为在m6A调控的OSCC自噬中潜在靶基因。在机制上，我们证实METTL14通过m6A-IGF2BP2依赖性的方式，通过甲基化RNA免疫沉淀逆转录实时聚合酶链式反应（meRIP-qPCR），RNA稳定性分析，突变分析和双荧光素酶报告实验，从转录后水平增强RB1CC1的表达，从而影响OSCC中的自噬和进展。综上所述，我们的发现表明，METTL14通过调节与自噬相关的基因RB1CC1的m6A修饰，作为OSCC的抑制剂，这可能为OSCC的诊断和治疗提供新的视角。2023年版权所有。

N6-methyladenosine (m6A) plays crucial roles in tumorigenesis and autophagy. However, the underlying mechanisms mediated by m6A and autophagy in the malignant progression of oral squamous cell carcinoma (OSCC) remain unclear. In this study, we revealed that downregulated expression of METTL14 was correlated with advanced clinicopathological characteristics and poor prognosis in OSCC. METTL14 knockdown significantly inhibited autophagy and facilitated malignant progression in vitro, and promoted tumor growth and metastasis in vivo. A cell model of rapamycin-induced autophagy was established to identify RB1CC1 as a potential target gene involved in m6A-regulated autophagy in OSCC, through RNA sequencing and methylated RNA immunoprecipitation sequencing (meRIP-seq) analysis. Mechanistically, we confirmed that METTL14 posttranscriptionally enhanced RB1CC1 expression in an m6A-IGF2BP2-dependent manner, thereby affecting autophagy and progression in OSCC, through methylated RNA immunoprecipitation qRT-PCR (meRIP-qPCR), RNA stability assays, mutagenesis assays and dual-luciferase reporter. Collectively, our findings demonstrated that METTL14 serves as an OSCC suppressor by regulating the autophagy-related gene RB1CC1 through m6A modification, which may provide a new insight for the diagnosis and therapy of OSCC.Copyright 2023 The Author(s).