Long non‐coding RNA GHET1 promotes gastric carcinoma cell proliferation by increasing c‐Myc mRNA stability

F Yang, X Xue, L Zheng, J Bi, Y Zhou, K Zhi… - The FEBS …, 2014 - Wiley Online Library
F Yang, X Xue, L Zheng, J Bi, Y Zhou, K Zhi, Y Gu, G Fang
The FEBS journal, 2014Wiley Online Library
Long non‐coding RNAs (lncRNAs), a recently characterized class of non‐coding RNAs,
have been shown to have important regulatory roles and are de‐regulated in a variety of
tumors. However, the contributions of lncRNAs to gastric carcinoma and their functional
mechanisms remain largely unknown. In this study, we found that lncRNA gastric carcinoma
high expressed transcript 1 (lncRNA‐GHET1) was up‐regulated in gastric carcinoma. The
over‐expression of this lncRNA correlates with tumor size, tumor invasion and poor survival …
Long non‐coding RNAs (lncRNAs), a recently characterized class of non‐coding RNAs, have been shown to have important regulatory roles and are de‐regulated in a variety of tumors. However, the contributions of lncRNAs to gastric carcinoma and their functional mechanisms remain largely unknown. In this study, we found that lncRNA gastric carcinoma high expressed transcript 1 (lncRNA‐GHET1) was up‐regulated in gastric carcinoma. The over‐expression of this lncRNA correlates with tumor size, tumor invasion and poor survival. Gain‐of‐function and loss‐of‐function analyses demonstrated that GHET1 over‐expression promotes the proliferation of gastric carcinoma cells in vitro and in vivo. 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. Depletion of c‐Myc abolishes the effects of GHET1 on 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 potential use of GHET1 for the prognosis and treatment of gastric carcinoma.
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