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首页> 外文期刊>The FEBS journal >Long non-coding RNA GHET1 promotes gastric carcinomacell proliferation by increasing c-Myc mRNA stability
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Long non-coding RNA GHET1 promotes gastric carcinomacell proliferation by increasing c-Myc mRNA stability

机译：长非编码RNA GHET1通过提高c-Myc mRNA稳定性来促进胃癌细胞增殖

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Long non-coding RNAs (lncRNAs), a recently characterized class of noncodingRNAs, have been shown to have important regulatory roles andare de-regulated in a variety of tumors. However, the contributions oflncRNAs to gastric carcinoma and their functional mechanisms remain largelyunknown. In this study, we found that lncRNA gastric carcinomahigh expressed transcript 1 (lncRNA-GHET1) was up-regulated in gastriccarcinoma. The over-expression of this lncRNA correlates with tumor size,tumor invasion and poor survival. Gain-of-function and loss-of-functionanalyses demonstrated that GHET1 over-expression promotes the proliferationof gastric carcinoma cells in vitro and in vivo. Knockdown of GHET1inhibits the proliferation of gastric carcinoma cells. RNA pull-down andimmunoprecipitation assays confirmed that GHET1 physically associateswith insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) andenhances the physical interaction between c-Myc mRNA and IGF2BP1,consequently increasing the stability of c-Myc mRNA and expression. Theexpression of GHET1 and c-Myc is strongly correlated in gastric carcinomatissues. Depletion of c-Myc abolishes the effects of GHET1 on proliferationof gastric carcinoma cells. Taken together, these findings indicatethat GHET1 plays a pivotal role in gastric carcinoma cell proliferation viaincreasing c-Myc mRNA stability and expression, which suggests potentialuse of GHET1 for the prognosis and treatment of gastric carcinoma.IntroductionGastric carcinoma is the fourth most frequent cancerand second most frequent cause of cancer-relateddeaths worldwide [1]. Despite efforts using diagnostictechniques and patient management, there has been littleprogress in improving the overall survival of gastriccarcinoma patients [2–4]. Development of suitabletherapy for the purpose of increasing survival has beenlimited because the pathophysiological mechanismscontributing to gastric carcinoma are largely unknown[5,6]. Therefore, revealing the molecular mechanismsfor development and progression of gastric carcinomais vital for developing effective therapies [7,8].Recently, studies using a combination of various genome-wide approaches, such as the ENCODE project,have shown that the majority of the mammalian genomeis transcribed, but only approximately 1.2% ofAbbreviationsEdU, ethynyl deoxyuridine; GHET1, gastric carcinoma high expressed transcript 1; GAPDH, glyceraldehyde 3-phosphate dehydrogenase;IGF2BP1, insulin-like growth factor 2 mRNA binding protein 1; lncRNA, long non-coding RNA; RIP, RNA immunoprecipitation.802 FEBS
机译：长非编码RNA（lncRNA）是近来表征的一类非编码RNA，已显示在多种肿瘤中具有重要的调节作用并且被失调。然而，lncRNA对胃癌的贡献及其功能机制仍然未知。在这项研究中，我们发现lncRNA胃癌高表达的转录本1（lncRNA-GHET1）在胃癌中被上调。该lncRNA的过表达与肿瘤大小，肿瘤浸润和不良的存活有关。功能获得和功能丧失分析表明，GHET1的过表达促进了体外和体内胃癌细胞的增殖。 GHET1的抑制抑制胃癌细胞的增殖。 RNA下拉和免疫沉淀分析证实GHET1与胰岛素样生长因子2 mRNA结合蛋白1（IGF2BP1）物理结合，并增强c-Myc mRNA和IGF2BP1之间的物理相互作用，从而提高c-Myc mRNA和表达的稳定性。 GHET1和c-Myc的表达在胃癌组织中高度相关。 c-Myc的消耗消除了GHET1对胃癌细胞增殖的影响。综上所述，这些发现表明GHET1通过增加c-Myc mRNA的稳定性和表达在胃癌细胞增殖中起关键作用，这提示GHET1在胃癌的预后和治疗中的潜在用途。世界范围内与癌症相关的死亡的原因[1]。尽管使用诊断技术和患者管理做出了努力，但在改善胃癌患者的总体生存方面进展甚微[2-4]。由于在很大程度上尚不清楚导致胃癌的病理生理机制，因此以增加存活率为目的的合适疗法的开发受到了限制[5,6]。因此，揭示胃癌发生和发展的分子机制对于开发有效的治疗方法至关重要[7,8]。最近，结合使用各种全基因组方法的研究（例如ENCODE项目）表明，大多数哺乳动物基因组被转录，但仅约1.2％的缩写EdU，乙炔基脱氧尿苷; GHET1，胃癌高表达转录本1; GAPDH，3-磷酸甘油醛脱氢酶; IGF2BP1，胰岛素样生长因子2 mRNA结合蛋白1; lncRNA，长非编码RNA; RIP，RNA免疫沉淀802 FEBS

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