METTL3 Promotes Esophageal Squamous Cell Carcinoma Metastasis Through Enhancing GLS2 Expression

Xiaoting Chen; Lanlan Huang; Tingting Yang; Jiexuan Xu; Chengyong Zhang; Zhendong Deng; Xiaorong Yang; Naihua Liu; Size Chen; Shaoqiang Lin

doi:10.3389/fonc.2021.667451

METTL3 Promotes Esophageal Squamous Cell Carcinoma Metastasis Through Enhancing GLS2 Expression

Front Oncol. 2021 May 19:11:667451. doi: 10.3389/fonc.2021.667451. eCollection 2021.

Authors

Xiaoting Chen¹, Lanlan Huang^{2

3}, Tingting Yang¹, Jiexuan Xu¹, Chengyong Zhang¹, Zhendong Deng⁴, Xiaorong Yang³, Naihua Liu², Size Chen⁵, Shaoqiang Lin^{1

5}

Affiliations

¹ Clinical Department of Guangdong Metabolic Disease Research Centre of Integrated Chinese and Western Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China.
² School of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
³ Clinical Laboratory, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China.
⁴ School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
⁵ Guangdong Provincial Engineering Research Center for Esophageal Cancer Precise Therapy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China.

Abstract

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.

Keywords: ESCC; GLS2; METTL3; m6A; metastasis.