Regulation of mRNA Stability in Human Saliva

研究mRNA在正常唾液和癌唾液中的表达和调控对于发现口腔癌的诊断标志物具有巨大的潜力。毫无疑问，唾液是最容易收集和保存的非侵入性体液-先前的研究表明，唾液中含有可用于口腔癌诊断生物标志物的人类mRNA。该技术是基于微阵列的，非常适合用于口腔病理学的实时医学诊断。该提案的目标是了解人类唾液中mRNA稳定性和去稳定性的作用。我们通过微阵列鉴定的大多数口腔癌基因在其3' UTR序列处含有富含AU的元件（战神）。战神靶向mRNA，通过其反式作用蛋白快速降解。因此，该提案的主要目的是确定唾液中的mRNA结合蛋白以及参与这一过程的因素。在癌症条件下，含有ARE的转录物在唾液中上调并稳定。因此，我们的假设是ARE转录物通过避免mRNA衰变机制在癌症条件下稳定。我们计划利用mRNA衰变系统沿着，结合我们之前对mRNA降解途径的研究所获得的专业知识，进一步测试、验证和鉴定唾液中mRNA稳定性的机制方面。本研究的主要目的是：（1）阐明影响人唾液中mRNA稳定性的因素。II）确定负责癌症患者唾液中mRNA稳定化的基本机制，III）证实含有ARE的mRNA衰变与MAP激酶/途径活化相关。总之，这些研究将打开正常和口腔癌中mRNA的稳定性，从而推动癌症中RNA生物标志物的临床诊断。

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. 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 gene's 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 proposal includes the following aim: I) Elucidate the factors involved in mRNA stability in human saliva. 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 lead to advances in clinical diagnostics of RNA biomarkers in cancer.