Cancer Res:长链非编码RNA在肺癌转移研究全新成果

2017-11-16 佚名 细胞

近日,上海交通大学医学院附属仁济医院上海市肿瘤研究所“癌基因及相关基因国家重点实验室”姚明研究组发表了题为“MetaLnc9 Facilitates Lung Cancer Metastasis via a PGK1-Activated AKT/mTOR Pathway”的研究论文,首次发现长链非编码RNA MetaLnc9在肺癌转移过程中的功能及分子机制,研究表明MetaLnc9是新的肺癌细胞转

近日,上海交通大学医学院附属仁济医院上海市肿瘤研究所“癌基因及相关基因国家重点实验室”姚明研究组发表了题为“MetaLnc9 Facilitates Lung Cancer Metastasis via a PGK1-Activated AKT/mTOR Pathway”的研究论文,首次发现长链非编码RNA MetaLnc9在肺癌转移过程中的功能及分子机制,研究表明MetaLnc9是新的肺癌细胞转移调控因子和潜在的治疗靶点。

这一研究成果发表于最新一期国际肿瘤研究领域权威期刊《癌症研究》(Cancer Research)。上海交通大学医学院附属仁济医院上海市肿瘤研究所“癌基因及相关基因国家重点实验室”姚明研究员和复旦大学附属肿瘤医院何祥火研究员为文章的通讯作者,第一作者分别为上海交通大学医学院博士研究生余涛和复旦大学附属肿瘤医院赵莹珺副研究员。

随着RNA测序技术的发展,成千上万种非编码转录本被发现存在于基因组中,过去认为这些非编码RNA是“进化上的垃圾”,然而越来越多的证据表明非编码RNA在众多生命活动和疾病中起重要作用。姚明团队经过多年的潜心研究,通过小鼠体内多次循环筛选成功建立了遗传背景相似,但细胞转移潜能不同的肺癌细胞系。该研究中,为了找到与非小细胞肺癌(NSCLC)转移相关的LncRNA,利用高低转移潜能的肺癌细胞系中进行了LncRNA表达谱芯片检测。余涛等人发现MetaLnc9在高转移细胞系SPC-A-1sci中表达显着上调,在73对肺癌临床样本检测和TCGA数据库464对临床样本分析中,发现高表达MetaLnc9与肺癌的TNM分期、肺癌转移及预后成正相关;在功能实验上,明确了MetaLnc9具有促进肺癌细胞的体外体内迁移和侵袭转移能力;在分子机制的研究中,MetaLnc9与糖酵解激酶PGK1相互作用并阻止其在肺癌细胞中的泛素化,导致致癌AKT / mTOR信号通路的激活。 MetaLnc9还与P54nrb / NonO(NONO)相互作用,以帮助介导CRTC的活化,CRTC是转录因子CREB的共同激活因子,加强了转移的正反馈环。这些研究表明MetaLnc9是新的肺癌细胞转移调控因子,有可能在肺癌预防和治疗中起到关键作用。

原始出处:

Yu T,et al.,MetaLnc9 Facilitates Lung Cancer Metastasis via a PGK1-Activated AKT/mTOR Pathway.Cancer Res. 2017 Nov 1;77(21):5782-5794.

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