microRNA signatures of tobacco carcinogen induced oral cancer

描述(由申请人提供)： 本研究旨在确定与口腔鳞状细胞癌(SCC)发生和发展相关的独特的microRNA信号。这些分子特征的获得将导致一系列新的生物标志物用于口腔鳞癌的早期检测。此外，还将探索microRNA-mRNA调控模块。我们在microRNA和mRNA水平上的观察结果的战略整合将促进在系统生物学水平上对这种疾病过程的整体理解。这项建议的另一个目标是建立一种动物模型，允许对口腔鳞状细胞癌疾病过程进行高通量基因组分析。大多数早期研究使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。在本研究中，我们将建立烟草致癌物诱导的小鼠口腔癌模型。我们的初步结果证明了该小鼠模型的可行性。这将使我们能够进行全基因组分析，并导致更好地了解这种疾病的发生和发展，以及识别用于口腔癌早期检测的生物标记物。为了实现这些目标，我们提出了两个特定的目标：第一个特定目标是建立生理性烟草致癌物诱发的小鼠口腔癌模型。这一小鼠模型将为我们提供一个独特的机会来研究口腔癌发生过程中microRNA的变化(以及其他全基因组研究)。具体目标2是确定口腔癌发生和发展的microRNA特征及其与mRNA表达模式的相关性。将使用统计和生物信息学方法来确定潜在的标记，并对其分类能力进行评估。还将识别和评估microRNA-mRNA调节模块。

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.