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UPF1 increases amino acid levels and promotes cell proliferation in lung adenocarcinoma via the eIF2α-ATF4 axis

UPF1通过调控eIF2α-ATF4通路提高细胞内氨基酸水平促进肺腺癌增殖

作     者:Lei FANG Huan QI Peng WANG Shiqing WANG Tianjiao LI Tian XIA Hailong PIAO Chundong GU Lei FANG;Huan QI;Peng WANG;Shiqing WANG;Tianjiao LI;Tian XIA;Hailong PIAO;Chundong GU

作者机构:Department of Thoracic SurgeryLung Cancer Diagnosis and Treatment Center of DalianThe First Affiliated Hospital of Dalian Medical UniversityDalian 116011China CAS Key Laboratory of Separation Science for Analytical ChemistryDalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China 

出 版 物:《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 (浙江大学学报(英文版)B辑(生物医学与生物技术))

年 卷 期:2022年第23卷第10期

页      面:863-875页

核心收录:

学科分类:1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基  金:supported by the National Natural Science Foundation of China(Nos.81803886 81774078 and 21907093) 

主  题:Up-frameshift 1(UPF1) Activating transcription factor 4(ATF4) Amino acid metabolism Lung adenocarcinoma 

摘      要:Up-frameshift 1(UPF1),as the most critical factor in nonsense-mediated messenger RNA(mRNA)decay(NMD),regulates tumor-associated molecular pathways in many ***,the role of UPF1 in lung adenocarcinoma(LUAD)amino acid metabolism remains largely *** this study,we found that UPF1 was significantly correlated with a portion of amino acid metabolic pathways in LUAD by integrating bioinformatics and *** further confirmed that UPF1 knockdown inhibited activating transcription factor 4(ATF4)and Ser51 phosphorylation of eukaryotic translation initiation factor 2α(eIF2α),the core proteins in amino acid metabolism *** addition,UPF1 promotes cell proliferation by increasing the amino-acid levels of LUAD cells,which depends on the function of ***,UPF1 mRNA expression is abnormal in LUAD tissues,and higher expression of UPF1 and ATF4 was significantly correlated with poor overall survival(OS)in LUAD *** findings reveal that UPF1 is a potential regulator of tumor-associated amino acid metabolism and may be a therapeutic target for LUAD.

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