单位：[1]Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Key Laboratory of Medical Immunology, Ministry of Health (Peking University), Beijing, 100191, P.R. China[2]Department of Clinical Laboratory, China-Japan Friendship Hospital, Beijing 100029, P.R. China[3]Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, P.R. China
Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3/IMP3/KOC), initially identified as an RNA-binding protein, is highly expressed in embryonic tissues and a variety of cancers. Previously, our group reported that IGF2BP3 may serve as a potential diagnostic marker for lung cancer. However, little is known about the function of IGF2BP3 in lung cancer development. Here we demonstrate that IGF2BP3 expression was markedly increased in lung cancer tissues compared to normal tissues at both mRNA and protein levels. Overexpression of IGF2BP3 in lung cancer cells promoted cell proliferation, tumor migration and invasion in vitro and in vivo, whereas knockdown of IGF2BP3 exhibited opposite effects. Notably IGF2BP3 was directly associated with a deubiquitinase Ubiquitin specific peptidase 10 (USP10) and attenuated its function in stabilizing p53 protein. Silencing IGF2BP3 expression in lung cancer cells consistently increased the half-life and protein level of p53 and induced G0/G1 arrest. Thus, our data together demonstrate that IGF2BP3 promotes lung tumorigenesis via attenuating p53 protein stability.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81301495]; China-Japan Friendship Hospital Youth Science and Technology Excellence Project [2014-QNYC-B-12]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2016M600017]; program for New Century Excellent Talents in UniversityProgram for New Century Excellent Talents in University (NCET)
第一作者单位：[1]Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Key Laboratory of Medical Immunology, Ministry of Health (Peking University), Beijing, 100191, P.R. China[2]Department of Clinical Laboratory, China-Japan Friendship Hospital, Beijing 100029, P.R. China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Zhao Wei,Lu Dan,Liu Liang,et al.Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) promotes lung tumorigenesis via attenuating p53 stability[J].ONCOTARGET.2017,8(55):93672-93687.doi:10.18632/oncotarget.21280.
医学