Open AccessFat mass and obesity‐associated protein regulates tumorigenesis of arecoline‐promoted human oral carcinoma
Author(s) -
Li Xia,
Xie Xiaoli,
Gu Yangcong,
Zhang Jianming,
Song Jiang,
Cheng Xiufeng,
Gao Yijun,
Ai Yilong
Publication year - 2021
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.4188
Subject(s) - arecoline , areca , cancer research , carcinogenesis , betel , downregulation and upregulation , medicine , transcription factor , cancer , pathological , carcinogen , oncology , biology , nut , biochemistry , receptor , gene , muscarinic acetylcholine receptor , structural engineering , engineering
Arecoline, a major alkaloid within areca nut extract, is recognized as the primary active carcinogen promoting oral squamous cell carcinoma (OSCC) pathological development. Dysregulation of N6‐methyladenosine (m6A) methyltransferase components (e.g., Fat mass and obesity‐associated protein [FTO] and methyltransferase‐like 3 [METTL3]) are closely associated with multiple cancer progression, including oral cancer. However, the biological function role of FTO in arecoline‐induced oral cancer is largely unknown. We identified that FTO was significantly upregulated in OSCC tissues from patients with areca nut chewing habits and chronic arecoline‐treated OSCC cell lines. Depletion of FTO attenuated the arecoline‐promoted stemness, chemoresistance, and oncogenicity of OSCC cells. Finally, we revealed that FTO was negatively regulated by a transcription factor forkhead box protein A2 (FOXA2) in OSCC cells. This study, for the first time, demonstrated that FTO plays an oncogenic role in arecoline‐induced OSCC progression. Thus, developing new therapeutic agents targeting FTO may serve as a promising method to treatment OSCC patients, especially those with areca nut chewing habits.