title: Long non-coding RNA GHET1 promotes gastric carcinoma cell proliferation by increasing c-Myc mRNA stability.
abstract: 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.
authors.affiliation: Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.forename: Xuchao
authors.initials: X
authors.lastname: Xue
authors.forename: Luming
authors.initials: L
authors.lastname: Zheng
authors.forename: Jianwei
authors.initials: J
authors.lastname: Bi
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Kangkang
authors.initials: K
authors.lastname: Zhi
authors.forename: Yan
authors.initials: Y
authors.lastname: Gu
authors.forename: Guoen
authors.initials: G
authors.lastname: Fang
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism* / Q000601:surgery; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020871:RNA Stability; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013270:Stomach / Q000601:surgery; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000601:surgery; D016019:Survival Analysis; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; C587667:GHET1 transcript, human; C406144:IGF2BP1 protein, human; C489427:MYC protein, human; D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins
keywords: c-Myc; gastric carcinoma; insulin-like growth factor 2 mRNA binding protein 1; long non-coding RNA; proliferation