N6-Methyladenosine RNA Demethylase FTO Promotes Gastric Cancer Metastasis by Down-Regulating the m6A Methylation of ITGB1

Frontiers in Oncology

Jiawen Xiao¹  Yizhe Wang³  Xiaofang Che⁵  Bowen Yang⁵  Ce Li⁵  Yunpeng Liu⁵  Wenqing Lu⁵  Yue Jin⁵  Xiujuan Qu⁵  Kezuo Hou⁵  Duo Wang⁵  Jianfei Qi⁷ 

[1] Department of Medical Oncology, Shenyang Fifth People Hospital, Shenyang, China;Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China;Department of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, Shenyang, China;Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China;Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China;Liaoning Province Clinical Research Center for Cancer, The First Hospital of China Medical University, Shenyang, China;Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, Baltimore, MD, United States;

关键词: FTO;    m6A;    gastric cancer;    metastasis;    ITGB1;   

DOI  :  10.3389/fonc.2021.681280

来源: DOAJ

【 摘 要 】

Abnormal RNA m6A methylation is known to lead to the occurrence and progression of multiple cancers including gastric cancer (GC). However, the integrative effects of all m6A methylation regulators on GC prognosis are unclear. Our research aimed to globally analyze the prognosis values of all 33 m6A RNA methylation regulators in GC by univariate and multivariate Cox regression analyses. Among all 33 m6A RNA methylation regulators, fat mass and obesity-associated protein (FTO), an m6A demethylase, was identified as a key prognostic risk factor on overall survival (OS) of GC patients. It was found that FTO could promote GC cell migration and invasion abilities, and we predicted that ITGB1 was a demethylated target of FTO. Knockdown (KD) of FTO significantly down-regulated ITGB1 expression at both mRNA and protein levels and augmented ITGB1 mRNA m6A modification level. Moreover, overexpression (OE) of ITGB1 could partially reverse FTO-KD-inhibited migration and invasion of GC cells. Our study found that FTO was an independent risk factor for overall survival (OS) of GC patients and FTO could promote GC metastasis by upregulating the expression of Integrin β1(ITGB1) via decreasing its m6A level. These results indicated that FTO can be a potent GC biomarker for prognosis prediction as well as a potential target in GC treatment.

【 授权许可】

Unknown