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

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.