MicroRNAs in the pathogenesis of Lung Cancer.
MicroRNAs in the pathogenesis of Lung Cancer.
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DOI：
10.1097/jto.0b013e3181a99c77
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发表时间：
2009-08
期刊：
影响因子：
--
通讯作者：
Nana-Sinkam SP
中科院分区：
文献类型：
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作者：
Wu X;Piper-Hunter MG;Crawford M;Nuovo GJ;Marsh CB;Otterson GA;Nana-Sinkam SP
肺癌是美国癌症相关死亡的主要原因。据估计，2008 年肺癌新诊断人数为 215,000 人，死亡人数为 163, 000 人。尽管出现了潜在的早期诊断和发现新型靶向疗法的新兴技术，但总体五年生存率仍然令人失望，只有 15%。生存率低的原因包括疾病出现较晚、缺乏早期检测标志物以及相似组织学分类的患者存在表型和基因型异质性。为了进一步了解肺癌的这种异质性和复杂性，研究人员应用了各种技术，包括基因组和蛋白质组的高通量分析。这些方法已经成功地识别出可以澄清肿瘤分子差异、识别新靶点和改善预后的特征。在过去十年中，研究人员发现了一种新的基因调控模式，即非编码 RNA，称为 microRNA（miRNA 或 miR）。 microRNA 是一种约 19-22 个核苷酸的单链 RNA，首先被确定对幼虫发育具有重要意义，它们通过诱导 mRNA 降解或抑制翻译来调节基因。 miRNA 参与多种细胞过程，包括细胞凋亡、发育、增殖和分化。通过同时调节数百个基因，miRNA 具有调节生物网络的能力。实体器官和血液恶性肿瘤中 miRNA 表达的整体变化表明它们在疾病发病机制中的重要性。迄今为止，肺癌的体内和体外研究均表明 miRNA 表达失调。此外，研究人员开始确定与肺肿瘤发生相关的 miRNA 的个体靶点和通路。因此，miRNA 可以识别关键靶点，并且在肺癌的发病机制中发挥重要作用。
Lung cancer is the leading cause of cancer related deaths in the United States. It is estimated that in 2008 there were 215,000 new diagnoses of lung cancer and 163, 000 deaths. Despite emerging technologies for potential early diagnosis and discovery of novel targeted therapies, the overall five year survival remains a disappointing 15%. Explanations for the poor survival include late presentation of disease, a lack of markers for early detection and both phenotypic and genotypic heterogeneity within patients of similar histological classification. In order to further understand this heterogeneity and thus complexity of lung cancer, investigators have applied various technologies including high throughput analysis of both the genome and proteome. Such approaches have been successful in identifying signatures that may clarify molecular differences in tumors, identify new targets and improve prognostication. In the last decade, investigators have identified a new mode of gene regulation in the form of non-coding RNAs termed microRNAs (miRNAs or miRs). First determined to be of importance in larval development, microRNAs are ~19–22 nucleotide single stranded RNAs that regulate genes by either inducing mRNA degradation or inhibiting translation. MiRNAs have been implicated in several cellular processes including apoptosis, development, proliferation and differentiation. By regulating hundreds of genes simultaneously, miRNAs have the capacity for regulation of biological networks. Global alterations in miRNA expression in both solid organ and haematological malignancies suggest their importance in the pathogenesis of disease. To date, both in vivo and in vitro studies in lung cancer demonstrate a dysregulation of miRNA expression. Furthermore, investigators are beginning to identify individual targets and pathways of miRNAs relevant to lung tumorigenesis. Thus, miRNAs may identify critical targets and be important in the pathogenesis of lung cancer.