Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) promotes lung tumorigenesis via attenuating p53 stability

Abstract

// Wei Zhao 1, 2, * , Dan Lu 3, * , Liang Liu 3 , Juan Cai 1 , Yu Zhou 1 , Ying Yang 1 , Yu Zhang 1 and Jun Zhang 1 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 Present address: 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 * These authors contributed equally to this work Correspondence to: Yu Zhang, email: zhangyu007@hsc.pku.edu.cn Jun Zhang, email: junzhang@bjmu.edu.cn Keywords: IGF2BP3, lung cancer, proliferation, USP10, p53 Received: November 25, 2016      Accepted: September 13, 2017      Published: September 27, 2017 ABSTRACT 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.