Frontiers in Oncology (Jul 2021)
N6-Methyladenosine RNA Demethylase FTO Promotes Gastric Cancer Metastasis by Down-Regulating the m6A Methylation of ITGB1
- Duo Wang,
- Duo Wang,
- Duo Wang,
- Duo Wang,
- Xiujuan Qu,
- Xiujuan Qu,
- Xiujuan Qu,
- Xiujuan Qu,
- Wenqing Lu,
- Wenqing Lu,
- Wenqing Lu,
- Wenqing Lu,
- Yizhe Wang,
- Yue Jin,
- Yue Jin,
- Yue Jin,
- Yue Jin,
- Kezuo Hou,
- Kezuo Hou,
- Kezuo Hou,
- Kezuo Hou,
- Bowen Yang,
- Bowen Yang,
- Bowen Yang,
- Bowen Yang,
- Ce Li,
- Ce Li,
- Ce Li,
- Ce Li,
- Jianfei Qi,
- Jiawen Xiao,
- Xiaofang Che,
- Xiaofang Che,
- Xiaofang Che,
- Xiaofang Che,
- Yunpeng Liu,
- Yunpeng Liu,
- Yunpeng Liu,
- Yunpeng Liu
Affiliations
- Duo Wang
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Duo Wang
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Duo Wang
- Liaoning Province Clinical Research Center for Cancer, The First Hospital of China Medical University, Shenyang, China
- Duo Wang
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Xiujuan Qu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Xiujuan Qu
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Xiujuan Qu
- Liaoning Province Clinical Research Center for Cancer, The First Hospital of China Medical University, Shenyang, China
- Xiujuan Qu
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Wenqing Lu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Wenqing Lu
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Wenqing Lu
- Liaoning Province Clinical Research Center for Cancer, The First Hospital of China Medical University, Shenyang, China
- Wenqing Lu
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Yizhe Wang
- Department of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, Shenyang, China
- Yue Jin
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Yue Jin
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Yue Jin
- Liaoning Province Clinical Research Center for Cancer, The First Hospital of China Medical University, Shenyang, China
- Yue Jin
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Kezuo Hou
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Kezuo Hou
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Kezuo Hou
- Liaoning Province Clinical Research Center for Cancer, The First Hospital of China Medical University, Shenyang, China
- Kezuo Hou
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Bowen Yang
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Bowen Yang
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Bowen Yang
- Liaoning Province Clinical Research Center for Cancer, The First Hospital of China Medical University, Shenyang, China
- Bowen Yang
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Ce Li
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Ce Li
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Ce Li
- Liaoning Province Clinical Research Center for Cancer, The First Hospital of China Medical University, Shenyang, China
- Ce Li
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Jianfei Qi
- Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, Baltimore, MD, United States
- Jiawen Xiao
- Department of Medical Oncology, Shenyang Fifth People Hospital, Shenyang, China
- Xiaofang Che
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Xiaofang Che
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Xiaofang Che
- Liaoning Province Clinical Research Center for Cancer, The First Hospital of China Medical University, Shenyang, China
- Xiaofang Che
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Yunpeng Liu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Yunpeng Liu
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Yunpeng Liu
- Liaoning Province Clinical Research Center for Cancer, The First Hospital of China Medical University, Shenyang, China
- Yunpeng Liu
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- DOI
- https://doi.org/10.3389/fonc.2021.681280
- Journal volume & issue
-
Vol. 11
Abstract
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.
Keywords
