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

项目摘要 尽管我们对microRNA（miRNA）在细胞凋亡中的重要作用的认识有了相当大的进步， 与癌症相关的基本细胞过程，大多数数据来自体外/动物模型或人群 研究范围有限。目前迫切需要对miRNA在乳腺癌中的作用进行系统的研究。 在精心设计的人群研究中，考虑到miRNA功能的复杂性， 乳腺癌的多因素性质。在此，我们设计了一个假设驱动的，技术支持的 该翻译项目旨在系统地阐明miRNA在乳腺癌生存中的作用。以 癌症基因组图谱（TCGA）和我们改进的深度测序的最新结果的优势 方法，我们将验证/鉴定代表性临床乳腺肿瘤中乳腺癌失调的miRNA。 亚型我们将采用多种体外试验来表征这些miRNAs在细胞中的潜力， 生长/增殖、分化和癌细胞的干细胞性，以及鉴定其下游靶点 在乳腺细胞系中。然后，我们将在一个基于人群的研究中独立验证实验室结果。 长岛乳腺癌研究项目（Long Island Breast Cancer Study Project，LIBCSP）独特的力量， 拟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（体外测定），其中可以表征候选miRNA的表型相关性， 经典流行病学（基于人群的研究），其中复杂的外源性因素和患者信息 可以考虑。这种多尺度、多学科和多方向的方法允许 更好地表征miRNA与乳腺癌发展之间的因果关系， 进展该项目具有真实的潜力，可以识别预测乳腺癌的miRNA特征。 癌症结果。

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.