microRNA signatures of tobacco carcinogen induced oral cancer

描述（由申请人提供）： 本研究旨在寻找与口腔鳞状细胞癌（SCC）发生和发展相关的microRNA特征。这些分子特征的获得将导致一组新的生物标志物，用于口腔SCC的早期检测。此外，microRNA-mRNA调控模块将被探索。我们在microRNA和mRNA水平上的观察结果的战略整合将在系统生物学水平上推进对这种疾病过程的整体理解。该提议的另一个目标是建立一种动物模型，其允许对口腔SCC疾病过程进行高通量基因组分析。大多数早期研究利用仓鼠模型来研究口腔癌。由于缺乏对仓鼠基因组的深入了解，只能对该模型进行有限的基因组分析。本研究拟建立烟草致癌物诱发的小鼠口腔癌模型。我们的初步结果证明了这种小鼠模型的可行性。这将使我们能够进行全基因组的基因组分析，并导致更好地了解这种疾病的发生和发展，以及识别用于早期检测口腔癌的生物标志物。具体目标1是建立生理性烟草致癌物诱导的小鼠口腔癌模型。这种小鼠模型将为我们提供独特的机会来研究口腔癌发生过程中microRNA的改变（以及其他全基因组研究）。具体目标2是鉴定microRNA特征及其与口腔癌发生和进展的mRNA表达模式的相关性。将使用统计学和生物信息学方法来识别潜在的标志物，并评估其分类能力。microRNA-mRNA调控模块也将被识别和评估。

DESCRIPTION (provided by applicant): This proposal aims to identify unique microRNA signatures that associated with the oral squamous cell carcinoma (SCC) initiation and progression. The attaining of these molecular signatures will lead to a set of novel biomarkers for the early detection of oral SCC. In addition, the microRNA-mRNA regulatory modules will be explored. The strategic integration of our observations at microRNA and mRNA levels will advance the overall understanding of this disease process at system biology level. An additional goal of this proposal is to establish an animal model that permits high throughput genomic analysis of the oral SCC disease process. Most of the early studies utilized a hamster model to study oral cancer. Due to the lack of in-depth knowledge on hamster genome, only limited genomic analyses can be performed on this model. In this study, we will establish a tobacco carcinogen induced oral cancer model in mice. Our preliminary results demonstrated the feasibility of this mouse model. This will enable us to perform genome-wide genomic analysis and lead to better understanding of the initiation and progression of this disease, as well as the identification of biomarkers for the early detection of oral cancer. Two specific aims were proposed to accomplish these objectives: The Specific Aim 1 is to establish a mouse oral cancer model induced with physiological tobacco carcinogen. This mouse model will provide us with unique opportunity to study alteration in microRNA (as well as other genome-wide studies) during the course of oral carcinogenesis. The Specific Aim 2 is to identify microRNA signatures and their correlation with mRNA expression patterns for oral cancer initiation and progression. Statistical and bioinformatic approaches will be used to identify potential markers and their classification power will be evaluated. The microRNA-mRNA regulatory modules will also be identified and evaluated.