Long noncoding RNAs (lncRNAs), a recently characterized class of noncoding RNAs, have been shown to have important regulatory roles and are deregulated in a variety of tumors. However, the contributions and functional mechanisms of lncRNAs to gastric carcinoma remain largely unknown.
In this study, researchers at the Shanghai Jiao Tong University School of Medicine, China found that lncRNA gastric carcinoma high expressed transcript 1 (lncRNA-GHET1) was upregulated in gastric carcinoma. The overexpression of this lncRNA correlates with tumor size, tumor invasion and poor survival. Gain-of-function and loss-of-function analyses demonstrated that GHET1 overexpression promotes the proliferation of gastric carcinoma cells in vitro and in vivo. The knockdown of GHET1 inhibits the proliferation of gastric carcinoma cells. RNA pull-down and immunoprecipitation assays confirmed that GHET1 physically associates with insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) and enhances the physical interaction between c-Myc mRNA and IGF2BP1, consequently increasing the stability of c-Myc mRNA and expression. The expression of GHET1 and c-Myc is strongly correlated in gastric carcinoma tissues. The depletion of c-Myc abolishes the effects of GHET1 on the proliferation of gastric carcinoma cells. Taken together, these findings indicate that GHET1 plays a pivotal role in gastric carcinoma cell proliferation via increasing c-Myc mRNA stability and expression, which suggests the potential use of GHET1 for the prognosis and treatment of gastric carcinoma.
- Yang F et al. (2013) Long noncoding RNA GHET1 promotes gastric carcinoma cell proliferation by increasing c-Myc mRNA stability. The FEBS Journal [Epub ahead of print]. [abstract]