FTO Facilitates Lung Adenocarcinoma Cell Progression by Activating Cell Migration Through mRNA Demethylation

• Main Authors: Ding Y, Qi N, Wang K, Huang Y, Liao J, Wang H, Tan A, Liu L, Zhang Z, Li J, Kong J, Qin S, Jiang Y
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-02-01
• Series: OncoTargets and Therapy
• Subjects: fto; lung adenocarcinoma; m6a demethylase
• Online Access: https://www.dovepress.com/fto-facilitates-lung-adenocarcinoma-cell-progression-by-activating-cel-peer-reviewed-article-OTT

Yudi Ding, 1,* Nana Qi, 2,* Ke Wang, 1,* Yiming Huang, 2 Jinling Liao, 1 Hongxue Wang, 3 Aihua Tan, 3 Lihua Liu, 1 Zhenqiang Zhang, 1 Jinlong Li, 1 Jinliang Kong, 1 Shouming Qin, 1 Yonghua Jiang 2, 4, 5 1Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 2Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 3Department of Chemotherapy, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 4Guangxi Key Laboratory of Genomic and Personalized Medicine, Nanning, Guangxi 530021, People’s Republic of China; 5Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi 530021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yonghua Jiang; Shouming Qin Tel [phone]Email [e-mail]; [e-mail]: The fat mass and obesity-associated protein (FTO) was identified as a critical demethylase involved in regulating cellular mRNA stability by removing N6-methyladenosine (m6A) residues from mRNA. Emerging evidence has revealed that FTO is deeply implicated in lung cancer. However, knowledge of the function of FTO in lung adenocarcinoma (LUAC) is limited.Methods: FTO and FTO R96Q (R96Q), an FTO missense mutant lacking demethylase activity, were ectopically overexpressed, and FTO was knocked down via siRNA in A549 and H1299 cells. The relationships between FTO with cell characteristics and mRNA m6A levels were explored. Furthermore, RNA sequencing was performed on A549 cells.Results: FTO overexpression enhanced the proliferation, migration, and invasion ability of A549 and H1299 cells, decreased mRNA m6A levels. Interestingly, overexpression of R96Q, blunted the effects of FTO overexpression on cell proliferation and invasion. Through RNA sequencing analysis of A549 cells overexpressing FTO or R96Q and control A594 cells, 45 genes were identified as affected by m6A mRNA demethylation. Most of these genes were related to lung cancer, such as laminin γ 2, thrombospondin 1, nerve growth factor inducible, integrin alpha11, and proprotein convertase subtilisin/kexin type 9. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested that these genes are fundamental to cancer development processes, such as cell migration and extracellular matrix organization.Conclusion: Our research shows that FTO facilitates LUAC cell progression by activating cell migration through m6A demethylation; however, further research on the mechanism underlying FTO activity in LUAC is necessary.Keywords: FTO, lung adenocarcinoma, m6A demethylase