MicroRNA Expression in Lung Cancer Development and Progression

肺癌发生和进展中的 MicroRNA 表达

基本信息

  • 批准号:
    7873350
  • 负责人:
  • 金额:
    $ 16.58万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-02-05 至 2012-01-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Lung cancer is the most frequent cause of cancer deaths in this country for both men and women. In 2009, 236,000 new cases and 163,000 deaths are estimated. The overall five year mortality has changed very little in the last two decades. Lung cancer represents a group of heterogeneous diseases that despite similar morphology exhibit different growth rates, metastatic potential and response to therapies. New targeted therapies such as epidermal growth factor inhibitors (EGFR) (Erlotinib and Gefitinib) have been successful in distinct subgroups of lung cancer patients. K-Ras exists downstream from EGFR signaling and approximately 30% of non-small cell lung cancers (adenocarcinomas) harbor K-Ras activation secondary to mutations. EGFR and K-Ras mutations represent very distinct subgroups of lung cancers with differing patterns of sensitivity and resistance to chemotherapeutic agents as well as potential differences in survival. K-Ras mutations tend to occur in former or active smokers while EGFR mutations are more common in never smokers. MicroRNAs (miRNAs) are a family of endogenous, small non-coding RNAs (approximately 21-25 nt long) expressed in many organisms. MiRNAs represent a newly discovered layer of gene regulation by targeting mRNA for degradation or inhibition of translation. A single miRNA may target several hundreds of genes. MiRNAs are integral to gene regulation, apoptosis, hematopoietic development, the maintenance of cell differentiation and may function as either tumor suppressors or oncogenes. We propose that a multi-platform approach that incorporates microRNA expression and target protein analysis both early and late in K-Ras related tumorigenesis as well as during regression will identify select miRNAs, critical biological pathways and potential targets for early diagnosis and treatment of lung cancer. We have two specific aims to our proposal: Specific Aim 1: Use a conditional murine model of K-Ras induction to define longitudinal patterns of miRNA expression that occur during tumor initiation, progression, establishment and regression and Specific Aim 2. Through the use of high throughput gene expression integrate miRNA and mRNA patterns of expression to identify key miRNA/target relationships and biological pathways that are relevant to K-Ras lung tumorigenesis PUBLIC HEALTH RELEVANCE: Lung cancer is the most frequent cause of cancer deaths in this country for both men and women. In 2009, 236,000 new cases and 163,000 deaths are estimated. This has resulted in tremendous societal and financial burden. Therefore, in addition to aggressive programs for tobacco cessation and more efficacious means of early detection, novel molecular approaches to understanding disease heterogeneity such as microRNA profiling will be important in our battle against this deadly disease.
描述(由申请人提供):肺癌是这个国家男性和女性癌症死亡的最常见原因。2009年,估计有236,000例新病例和163,000例死亡。在过去的二十年里,五年死亡率总体变化不大。肺癌代表一组异质性疾病,尽管形态相似,但表现出不同的生长速率、转移潜力和对治疗的反应。新的靶向治疗,如表皮生长因子抑制剂(EGFR)(厄洛替尼和吉非替尼)已在不同的肺癌患者亚组中取得成功。K-Ras存在于EGFR信号传导的下游,并且约30%的非小细胞肺癌(腺癌)具有继发于突变的K-Ras活化。EGFR和K-Ras突变代表了非常不同的肺癌亚组,它们对化疗药物的敏感性和耐药性模式不同,生存率也存在潜在差异。K-Ras突变倾向于发生在前吸烟者或活跃吸烟者中,而EGFR突变在从不吸烟者中更常见。 微小RNA(microRNAs,miRNAs)是一类内源性小分子非编码RNA(长度约21-25 nt),广泛存在于多种生物体中。miRNAs代表了一个新发现的基因调控层,通过靶向mRNA降解或抑制翻译。一个miRNA可以靶向数百个基因。miRNA是基因调控、细胞凋亡、造血发育、细胞分化维持的组成部分,并且可以作为肿瘤抑制因子或癌基因发挥作用。 我们提出一种多平台方法,该方法在K-Ras相关肿瘤发生的早期和晚期以及在消退期间结合microRNA表达和靶蛋白分析,将确定选择的miRNA,关键生物学途径和肺癌早期诊断和治疗的潜在靶点。我们的建议有两个具体目标:具体目标1:使用K-Ras诱导的条件性小鼠模型来定义肿瘤起始、进展、建立和消退期间发生的miRNA表达的纵向模式,以及具体目标2。通过使用高通量基因表达,整合miRNA和mRNA表达模式,以鉴定与K-Ras肺肿瘤发生相关的关键miRNA/靶标关系和生物学途径 公共卫生相关性:肺癌是这个国家男性和女性癌症死亡的最常见原因。2009年,估计有236,000例新病例和163,000例死亡。这造成了巨大的社会和财政负担。因此,除了积极的戒烟计划和更有效的早期检测手段外,了解疾病异质性的新分子方法(如microRNA分析)在我们与这种致命疾病的斗争中将非常重要。

项目成果

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SERGE PATRICK NANASINKAM其他文献

SERGE PATRICK NANASINKAM的其他文献

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{{ truncateString('SERGE PATRICK NANASINKAM', 18)}}的其他基金

CTSA K12 Program at Virginia Commonwealth University
弗吉尼亚联邦大学 CTSA K12 项目
  • 批准号:
    10619075
  • 财政年份:
    2023
  • 资助金额:
    $ 16.58万
  • 项目类别:
Project 1: Lung Cancer
项目一:肺癌
  • 批准号:
    10493289
  • 财政年份:
    2021
  • 资助金额:
    $ 16.58万
  • 项目类别:
Project 1: Lung Cancer
项目一:肺癌
  • 批准号:
    10290161
  • 财政年份:
    2021
  • 资助金额:
    $ 16.58万
  • 项目类别:
Institutional Career Development Core
机构职业发展核心
  • 批准号:
    10409658
  • 财政年份:
    2018
  • 资助金额:
    $ 16.58万
  • 项目类别:
Institutional Career Development Core
机构职业发展核心
  • 批准号:
    9913602
  • 财政年份:
    2018
  • 资助金额:
    $ 16.58万
  • 项目类别:
MicroRNA Expression in Lung Cancer Development and Progression
肺癌发生和进展中的 MicroRNA 表达
  • 批准号:
    8021770
  • 财政年份:
    2010
  • 资助金额:
    $ 16.58万
  • 项目类别:
Integration of transcriptosome and microRNome in Understanding COPD Phenotypes
转录体和 microRNome 的整合在理解 COPD 表型中的作用
  • 批准号:
    7690864
  • 财政年份:
    2008
  • 资助金额:
    $ 16.58万
  • 项目类别:
Regulation of Prostacyclin in Pulmonary Hypertension
前列环素在肺动脉高压中的调节
  • 批准号:
    6933068
  • 财政年份:
    2004
  • 资助金额:
    $ 16.58万
  • 项目类别:
Regulation of Prostacyclin in Pulmonary Hypertension
前列环素在肺动脉高压中的调节
  • 批准号:
    6817114
  • 财政年份:
    2004
  • 资助金额:
    $ 16.58万
  • 项目类别:
Regulation of Prostacyclin in Pulmonary Hypertension
前列环素在肺动脉高压中的调节
  • 批准号:
    7480211
  • 财政年份:
    2004
  • 资助金额:
    $ 16.58万
  • 项目类别:

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