MicroRNA & Breast Cancer: Functional Characterization in a Population-Based Study

项目摘要 尽管我们对microRNA(MiRNA)在体内的重要作用的了解有了很大的进步 与癌症相关的基本细胞过程，大多数数据来自体外/动物模型或种群 研究范围有限。目前迫切需要对miRNA在乳房中的作用进行系统研究。 设计良好的人群研究中的癌症，考虑到miRNA功能和 乳腺癌的多因素性质。在这里，我们设计了一种假设驱动的、技术使能的 翻译项目旨在系统地阐明miRNA在乳腺癌生存中的作用。拿走 肿瘤基因组图谱(TCGA)的最新结果和我们改进的深度测序的优势 方法，我们将验证/鉴定乳腺癌中具有代表性的临床肿瘤中表达异常的miRNAs。 子类型。我们将使用多种体外实验来鉴定这些miRNAs在细胞中的潜力。 生长/增殖、分化和癌细胞干细胞，以及确定其下游靶点 在乳腺细胞系中。然后，我们将独立验证实验室的发现，在一个以人口为基础的 流行病学研究，长岛乳腺癌研究项目(LIBCSP)。独一无二的实力 建议的研究是我们将最新的基因组技术(深度测序)、功能分子 方法(体外分析)，其中候选miRNAs的表型相关性可以用 经典流行病学(以人群为基础的研究)，其中包括复杂的外部因素和患者信息 可以被考虑在内。这种多规模、多学科和多方向的方法允许 更好地表征miRNA与乳腺癌发生和发展之间的因果关系 进步。这个项目真正有可能识别出预测乳房的miRNA签名。 癌症后果。

Project Summary Despite considerable advancement in our knowledge about the significant role of microRNA (miRNA) in fundamental cellular processes related to cancer, most data come from in vitro/animal models or population studies with limited scope. There is a critical need for systematic investigation on the role of miRNA in breast cancer in well-designed population studies that take into account the complexity of miRNA functions and multifactorial nature of breast cancer. Herein, we have designed a hypothesis-driven, technology-enabled translational project aimed at systematically elucidating the role of miRNA in breast cancer survival. Taking advantage of the latest results from the Cancer Genome Atlas (TCGA) and our improved deep sequencing method, we will validate/identify breast cancer dysregulated miRNAs in breast tumors of representative clinical subtypes. We will employ multiple in vitro assays to characterize these miRNAs for their potential in cell growth/proliferation, differentiation, and cancer cell stemness, as well as to identify their down-stream targets in breast cell lines. We will then independently validate the laboratory findings in a population-based epidemiologic study, the Long Island Breast Cancer Study Project (LIBCSP). The unique strength of the proposed study is our ability to incorporate latest genomic technology (deep sequencing), functional molecular methods (in vitro assays), in which phenotypic relevance of candidate miRNAs can be characterized, with classic epidemiology (population-based study), in which complex exogenous factors and patient information can be taken into account. This multi-scale, multi-disciplinary, and multi-directional approach allows a better characterization of the causal relationship between miRNA and breast cancer development and progression. This project has the real potential to identify a miRNA signature that predicts breast cancer outcomes.