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.

Public Health Relevance

): Oral cancer is one of the most devastating cancers. This study utilizes innovative approaches to identify biomarkers for early diagnosis of oral cancer and potential therapeutic targets for cancer prevention from a pool of novel nucleic acid molecules (microRNA).

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
5R03CA135992-02
Application #
7817181
Study Section
Special Emphasis Panel (ZCA1-SRLB-F (J1))
Program Officer
Krueger, Karl E
Project Start
2009-05-01
Project End
2012-04-30
Budget Start
2010-05-01
Budget End
2012-04-30
Support Year
2
Fiscal Year
2010
Total Cost
$78,500
Indirect Cost
Name
University of Illinois at Chicago
Department
Dentistry
Type
Schools of Dentistry
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
Chen, Zujian; Yu, Tianwei; Cabay, Robert J et al. (2017) miR-486-3p, miR-139-5p, and miR-21 as Biomarkers for the Detection of Oral Tongue Squamous Cell Carcinoma. Biomark Cancer 9:1-8
Jin, Yi; Chen, Zujian; Liu, Xiqiang et al. (2013) Evaluating the microRNA targeting sites by luciferase reporter gene assay. Methods Mol Biol 936:117-27
Liu, Zhonghua; Li, Su; Cai, Yuchen et al. (2012) Manganese superoxide dismutase induces migration and invasion of tongue squamous cell carcinoma via H2O2-dependent Snail signaling. Free Radic Biol Med 53:44-50
Wang, Cheng; Liu, Xiqiang; Huang, Hongzhang et al. (2012) Deregulation of Snai2 is associated with metastasis and poor prognosis in tongue squamous cell carcinoma. Int J Cancer 130:2249-58
Chen, Zujian; Jin, Yi; Yu, Dongsheng et al. (2012) Down-regulation of the microRNA-99 family members in head and neck squamous cell carcinoma. Oral Oncol 48:686-91
Jin, Yi; Wang, Cheng; Liu, Xiqiang et al. (2011) Molecular characterization of the microRNA-138-Fos-like antigen 1 (FOSL1) regulatory module in squamous cell carcinoma. J Biol Chem 286:40104-9
Wang, Cheng; Liu, Xiqiang; Chen, Zujian et al. (2011) Polycomb group protein EZH2-mediated E-cadherin repression promotes metastasis of oral tongue squamous cell carcinoma. Mol Carcinog :
Wang, Cheng; Huang, Hongzhang; Huang, Zhiquan et al. (2011) Tumor budding correlates with poor prognosis and epithelial-mesenchymal transition in tongue squamous cell carcinoma. J Oral Pathol Med 40:545-51
Sharma, Sanjai; Liao, Wei; Zhou, Xiaofeng et al. (2011) Exon 11 skipping of E-cadherin RNA downregulates its expression in head and neck cancer cells. Mol Cancer Ther 10:1751-9
Jiang, Lu; Dai, Yang; Liu, Xiqiang et al. (2011) Identification and experimental validation of G protein alpha inhibiting activity polypeptide 2 (GNAI2) as a microRNA-138 target in tongue squamous cell carcinoma. Hum Genet 129:189-97

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