Regulation of mRNA Stability in Human Saliva

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DESCRIPTION (provided by applicant): Studying expression and regulation of mRNA in normal versus cancer saliva is garnering great potential for the discovery of diagnostic marker for oral cancer. Undoubtedly, saliva is the most non-invasive body fluid that can be easily collected and preserved. Previous research has shown that saliva contains human mRNAs that can be used for diagnostic biomarkers for oral cancer. Dr. David Wong's research group at the University of California Los Angeles, School of Dentistry, has recently developed diagnostic RNA markers in oral cancer patient saliva. This technology is a microarray based and well suited for real-time medical diagnostics for oral pathology. The goal of this proposal is directed toward understanding the role of mRNA stability and de-stability in human saliva. The majority of oral cancer genes which we identified through microarray contain AU-rich elements (AREs) at their 3' UTR sequences. AREs target mRNAs for rapid degradation via its trans-acting proteins. Hence the main aim of this proposal is to identify mRNA binding proteins in saliva and what factors are involved in this process. Under cancer conditions ARE containing transcripts are up-regulated and stabilized in saliva. Thus, our hypothesis is that ARE transcripts are stabilized in cancer conditions by means of avoiding mRNA decay machinery. We plan to utilize mRNA decay system along with expertise gained from our previous studies on mRNA degradation pathways so far to further test, validate and identify the mechanistic aspects of mRNA stability in saliva. The initial mentored phase of this .proposal includes the following aim: I) Elucidate the factors involved in mRNA stability in human saliva. The independent investigator phase includes the following aims: II) Determine the fundamental mechanism responsible for the stabilization of mRNA's in saliva of cancer patients, III) Validate the ARE containing mRNA decay in correlation with MAP kinase/pathway activation. In summary, these studies will open up the mRNA stability in normal and oral cancer saliva lead to advances in clinical diagnostics of RNA biomarkers in cancer.