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m(6)A RNA modification modulates PI3K/Akt/mTOR signal pathway in Gastrointestinal Cancer

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收录情况： ◇ SCIE

作者：
Qijie Zhao[1,2,3] ; Yueshui Zhao[1,2] ; Wei Hu[4,5] ; Yan Zhang[6] ; Xu Wu[1,2] ; Jianwei Lu[6] ; Mingxing Li[1,2] ; Wei Li[7,8] ; Weiqing Wu[8] ; Jianhong Wang[7,8] ; Fukuan Du[1,2] ; Huijiao Ji[1,2] ; Xiao Yang[1] ; Zhenyu Xu[9] ; Lin Wan[10] ; Qinglian Wen[11] ; Xiang Li[1] ; Chi Hin Cho[1,2] ; Chang Zou[7,8,*2] ; Jing Shen[1,2,*1] ; Zhangang Xiao[1,2,*1] ;
机构： [1]Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China. [2]South Sichuan Institute of Translational Medicine, Luzhou, 646000, Sichuan, PR China. [3]Department of Pathophysiology, College of Basic Medical Science, Southwest Medical University, Luzhou, 646000, Sichuan, PR China. [4]Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, PR China. [5]Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong SAR, PR China. [6]Department of Oncology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210000, PR China. [7]Clinical Medical Research Center, the Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University, Shenzhen People’s Hospital, Shenzhen, Guangdong 518020, PR China. [8]Department of Breast and Thyroid Surgery, the Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University, Shenzhen People’s Hospital, Shenzhen, Guangdong 518020, PR China. [9]Department of Pharmacy, Yijishan Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, PR China. [10]Department of Hematology and Oncology, The Children’s Hospital of Soochow, Jiangsu, PR China. [11]Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, PR China
出处：
DOI： 10.7150/thno.42971
ISSN：

关键词： m(6)A RNA methylation gastrointestinal cancer bioinformatics PI3K/Akt signal pathway mTOR signaling pathway

摘要：
Rationale: Methylation at the N6 position of adenosine (m(6)A) is the most prevalent RNA modification within protein-coding mRNAs in mammals, and it is a reversible modification with various important biological functions. The formation and function of m(6)A are regulated by methyltransferases (writers), demethylases (erasers), and special binding proteins (readers) as key factors. However, the underlying modification mechanisms of m(6)A in gastrointestinal (GI) cancer remain unclear. Here, we performed comprehensive molecular profiling of the nine known m(6)A writer, eraser, and reader proteins in GI cancer. Methods: Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were used. Gene alteration and pathway analysis were done in cBioportal. The protein network of m(6)A regulators and its related pathway members was analyzed in STRING online platform. Phylogenetic tree was constructed in MEGA7. m(6)A modification sites were predicted by SRAMP. m6A related SNPs were analyzed by m(6)ASNP. The modulation of m(6)A on its related pathway members was validated by m(6)A-seq, real-time PCR and phosphor-MAPK array. Results: We found that m(6)A regulators were mostly upregulated in GI cancer and their differential expression significantly influenced the overall survival of patients with GI cancer. The phosphatidylinositol-3-kinase (PI3K)/Akt and mammalian target of rapamycin (mTOR) signaling pathways were found to be potentially affected by m(6)A modification in most human cancers, including GI cancer, which was further verified by m(6)A-Seq and phospho-MAPK array. Conclusions: Our findings suggest that m(6)A RNA modification has a fundamental role in the regulation of PI3K/Akt and mTOR signaling pathway function in cancer.

基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81503093, 81602166, 81672444]; Southwest Medical University Luzhou [2016LZXNYD-T01, 2017LZXNYD-Z05, 2017LZXNYD-J09, 2019LZXNYD-J45]
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外文
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中科院(CAS)分区：
出版当年[2020]版：
大类 | 1 区 医学
小类 | 1 区 医学：研究与实验
最新[2023]版：
大类 | 1 区 医学
小类 | 1 区 医学：研究与实验
JCR分区：
出版当年[2020]版：
Q1 MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版：
Q1 MEDICINE, RESEARCH & EXPERIMENTAL

影响因子： 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

第一作者：
第一作者机构： [1]Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China. [2]South Sichuan Institute of Translational Medicine, Luzhou, 646000, Sichuan, PR China. [3]Department of Pathophysiology, College of Basic Medical Science, Southwest Medical University, Luzhou, 646000, Sichuan, PR China.
共同第一作者：
通讯作者：
通讯机构： [1]Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China. [2]South Sichuan Institute of Translational Medicine, Luzhou, 646000, Sichuan, PR China. [7]Clinical Medical Research Center, the Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University, Shenzhen People’s Hospital, Shenzhen, Guangdong 518020, PR China. [8]Department of Breast and Thyroid Surgery, the Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University, Shenzhen People’s Hospital, Shenzhen, Guangdong 518020, PR China. [*1]Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China [*2]Clinical Medical Research Center, the Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University, Shenzhen People’s Hospital, Shenzhen, Guangdong 518020, P.R. China
推荐引用方式(GB/T 7714)：
Qijie Zhao,Yueshui Zhao,Wei Hu,et al.m(6)A RNA modification modulates PI3K/Akt/mTOR signal pathway in Gastrointestinal Cancer[J].THERANOSTICS.2020,10(21):9528-9543.doi:10.7150/thno.42971.
APA：
Qijie Zhao,Yueshui Zhao,Wei Hu,Yan Zhang,Xu Wu...&Zhangang Xiao.(2020).m(6)A RNA modification modulates PI3K/Akt/mTOR signal pathway in Gastrointestinal Cancer.THERANOSTICS,10,(21)
MLA：
Qijie Zhao,et al."m(6)A RNA modification modulates PI3K/Akt/mTOR signal pathway in Gastrointestinal Cancer".THERANOSTICS 10..21(2020):9528-9543

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