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

微小RNA

基本信息

批准号：
8912879
负责人：
Jia Chen
金额：
$ 64.24万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-30 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8912879
关键词：
Accounting Animal Model Apoptosis Archives Biological Assay Biological Markers Breast Breast Cancer Cell Cancer Prognosis Candidate Disease Gene Cell Death Cell Line Cell Proliferation Cell physiology Cells Characteristics Chemopreventive Agent Classification Clinical Complex Custom DNA Methylation Data Databases Development Diet Disease Epidemiologic Studies Epidemiology Etiology Exogenous Factors Functional disorder Gene Expression Regulation Gene Targeting Genetic Predisposition to Disease Genome Genomics Guilt In Vitro Investigation Knowledge Laboratory Finding Lead Life Style Link Long Island Breast Cancer Study Malignant Neoplasms Mammary Neoplasms Messenger RNA Methods MicroRNAs Molecular Molecular Profiling Nature Neoplasm Metastasis Oncogenic Outcome Pathogenesis Patients Phenotype Population Population Study Post-Transcriptional Regulation Process Prognostic Marker Public Health Publications Reproductive History Research Design Role Sample Size Sampling Source Stream System Technology The Cancer Genome Atlas Therapeutic Time Tumor Suppressor Proteins Tumor Tissue Validation base breast tumorigenesis cancer cell cancer cell differentiation cancer diagnosis cancer genome cell growth deep sequencing design follow-up gene discovery histone modification improved in vitro Assay infancy malignant breast neoplasm matrigel novel population based public health relevance reconstruction stem stemness treatment strategy tumor tumor initiation tumor progression

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：尽管我们对 microRNA (miRNA) 在与癌症相关的基本细胞过程中的重要作用的认识有了相当大的进步，但大多数数据来自范围有限的体外/动物模型或群体研究。迫切需要在精心设计的群体研究中系统地研究 miRNA 在乳腺癌中的作用，并考虑到 miRNA 功能的复杂性和乳腺癌的多因素性质。在此，我们设计了一个假设驱动、技术支持的转化项目，旨在系统地阐明 miRNA 在乳腺癌生存中的作用。利用癌症基因组图谱 (TCGA) 的最新结果和我们改进的深度测序方法，我们将验证/鉴定代表性临床亚型乳腺肿瘤中乳腺癌失调的 miRNA。我们将采用多种体外测定来表征这些 miRNA 在细胞生长/增殖、分化和癌细胞干性方面的潜力，并确定它们在乳腺细胞系中的下游靶标。然后我们将独立验证实验室研究结果一项基于人群的流行病学研究，即长岛乳腺癌研究项目 (LIBCSP)。拟议研究的独特优势在于我们能够将最新的基因组技术（深度测序）、功能分子方法（体外测定）与经典流行病学（基于人群的研究）相结合，其中可以表征候选 miRNA 的表型相关性，其中可以考虑复杂的外源因素和患者信息。这种多尺度、多学科、多方向的方法可以更好地表征 miRNA 与乳腺癌发生和进展之间的因果关系。该项目具有识别预测乳腺癌结果的 miRNA 特征的真正潜力。