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Published on: October 27, 2014
Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) promotes lung tumorigenesis via attenuating p53
Wei Zhao1,2, Dan Lu3, Liang Liu3
1Department 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.
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.
Insights
Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) promotes lung cancer by reducing p53 stability. This study reveals IGF2BP3
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) is highly expressed in embryonic tissues and cancers.
- IGF2BP3 is a potential diagnostic marker for lung cancer, but its function in lung tumorigenesis is unclear.
Purpose of the Study:
- To investigate the functional role of IGF2BP3 in lung cancer development.
- To elucidate the molecular mechanism by which IGF2BP3 influences lung tumorigenesis.
Main Methods:
- Quantitative analysis of IGF2BP3 mRNA and protein levels in lung cancer tissues versus normal tissues.
- In vitro and in vivo experiments assessing the effects of IGF2BP3 overexpression and knockdown on lung cancer cell behavior.
- Investigation of the interaction between IGF2BP3 and USP10, and its impact on p53 protein stability.
Main Results:
- IGF2BP3 expression is significantly upregulated in lung cancer tissues at both mRNA and protein levels.
- Overexpression of IGF2BP3 enhances lung cancer cell proliferation, migration, and invasion, while knockdown inhibits these processes.
- IGF2BP3 interacts with USP10, attenuating p53 protein stability, leading to increased p53 half-life and protein levels upon IGF2BP3 silencing, and inducing G0/G1 cell cycle arrest.
Conclusions:
- IGF2BP3 promotes lung tumorigenesis by inhibiting p53 protein stability through interaction with USP10.
- Targeting IGF2BP3 may represent a potential therapeutic strategy for lung cancer.
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