DataSheet_1_METTL3 Promotes Esophageal Squamous Cell Carcinoma Metastasis Through Enhancing GLS2 Expression.xlsx

Recent studies have identified pleiotropic roles of methyltransferase-like 3 (METTL3) in tumor progression. However, the roles of METTL3 in esophageal squamous cell carcinoma (ESCC) are still unclear. Here, we investigated the function and mechanism of METTL3 in ESCC tumorigenesis. We reported that higher METTL3 expression was found in ESCC tissues and was markedly associated with depth of invasion and poor prognosis. Loss- and gain-of function studies showed that METTL3 promoted the migration and invasion of ESCC cells in vitro. Integrated methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and RNA sequencing (RNA-Seq) analysis first demonstrated that glutaminase 2 (GLS2) was regulated by METTL3 via m6A modification. Our findings identified METTL3/GLS2 signaling as a potential therapeutic target in antimetastatic strategies against ESCC.

近期研究已揭示甲基转移酶样3（methyltransferase-like 3, METTL3）在肿瘤进展中的多效性作用。然而，METTL3在食管鳞状细胞癌（esophageal squamous cell carcinoma, ESCC）中的作用仍不明确。本研究探讨了METTL3在食管鳞状细胞癌发生发展中的功能与机制。我们发现，METTL3在食管鳞状细胞癌组织中呈高表达，且与肿瘤侵袭深度及不良预后显著相关。功能缺失与功能获得性实验证实，METTL3可在体外促进食管鳞状细胞癌细胞的迁移与侵袭。整合甲基化RNA免疫沉淀测序（methylated RNA immunoprecipitation sequencing, MeRIP-Seq）与RNA测序（RNA sequencing, RNA-Seq）的分析结果首次表明，谷氨酰胺酶2（glutaminase 2, GLS2）可通过m6A修饰受METTL3调控。本研究结果证实，METTL3/GLS2信号通路可作为食管鳞状细胞癌抗转移治疗的潜在靶点。