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.
Highlights
Lung cancer is the leading cause of cancer related mortality worldwide [1]
Elevated IGF2BP3 DNA copy numbers were observed in lung adenocarcinoma, squamous cell lung carcinoma, and mixed types of lung cancer compared to normal lung tissues in TCGA lung dataset and Weiss lung dataset (Supplementary Figure 1A and 1B)
Elevated IGF2BP3 mRNA levels were observed in adenocarcinoma, squamous cell carcinoma and large cell carcinoma compared to normal lung tissues in the Hou and Landi lung datasets, respectively (Supplementary Figure 1C and 1D)
Summary
Lung cancer is the leading cause of cancer related mortality worldwide [1]. Lung cancer has two major types: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Most lung cancers (85%) are NSCLC, which can be further divided into adenocarcinoma (ADC), squamous cell carcinoma (SCC) and large cell carcinoma (LCLC) [2, 3]. Surgical resection and chemotherapy represent the major therapeutic means for lung cancer, most lung cancer patients may be inoperable at the time of being diagnosed with advanced disease grading and metastasis at regional or distal sites. Understanding the contributors and identification of novel therapeutic targets in lung tumorigenesis may facilitate the development of novel drugs for lung cancer therapy
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