Regulation of mRNA Stability in Human Saliva

人类唾液中 mRNA 稳定性的调节

• 批准号: 7879998
• 负责人: Viswanathan Palanisamy
• 金额: $ 24.65万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7879998
• 关键词: 3' Untranslated Regions; Binding Proteins; Biological Markers; Body Fluids; Cancer Patient; Clinical; Colon Carcinoma; Data; Degradation Pathway; Development; Diagnostic; Disease; ERG gene; Elements; Family; Gene Expression; Gene Expression Regulation; Genes; Glioma; Goals; Hand; Human; IL8 gene; In Vitro; Indium; Knowledge; Laboratories; Lead; MAP Kinase Activation Pathway; Malignant Neoplasms; Medical; Mentors; Messenger RNA; Microarray Analysis; Mitogen-Activated Protein Kinases; Modeling; Oncogenes; Pathway interactions; Phase; Play; Process; Protein Binding; Proteins; Proto-Oncogenes; Publishing; RNA; RNA-Binding Proteins; Regulation; Research; Research Personnel; Role; Saliva; Salivary; Series; Specific qualifier value; System; Technology; Testing; Time; Transcript; Viral; Work; base; cancer cell; cytokine; experience; insight; mRNA Decay; mRNA Expression; mRNA Stability; mRNA Transcript Degradation; malignant mouth neoplasm; member; mitogen-activated protein kinase p38; research study

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.

研究mRNA在正常与癌症中的表达和调节是发现口腔癌诊断标记物的巨大潜力。毫无疑问，唾液是可以轻松收集和保存的最无创的体液 - 先前的研究表明，唾液中包含可用于口腔癌诊断生物标志物的人类mRNA。该技术是一种基于微阵列的，非常适合口腔病理的实时医学诊断。该提案的目的是针对理解mRNA稳定性和去稳定性在人类唾液中的作用。我们通过微阵列确定的大多数口腔癌基因在其3'UTR序列中包含富含AU的元素（ARE）。 ARES靶向mRNA通过其反式蛋白质快速降解。因此，该提案的主要目的是鉴定唾液中的mRNA结合蛋白以及此过程中涉及哪些因素。在癌症条件下，包含转录本在唾液中被上调和稳定。因此，我们的假设是通过避免mRNA衰减机制在癌症条件下稳定转录本。我们计划利用mRNA衰变系统以及从先前关于mRNA降解途径的研究获得的专业知识，以进一步测试，验证和确定唾液中mRNA稳定性的机械方面。该提案包括以下目的：i）阐明人类唾液中mRNA稳定性的因素。 ii）确定导致癌症患者唾液中mRNA稳定的基本机制，iii）验证该mRNA含有与MAP激酶/途径激活相关的mRNA衰变。总而言之，这些研究将在正常和口腔癌中开放mRNA稳定性，从而导致癌症RNA生物标志物的临床诊断方面的进步。