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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Transition Award (R00)
Project #
5R00DE018165-05
Application #
8044130
Study Section
Special Emphasis Panel (NSS)
Program Officer
Burgoon, Penny W
Project Start
2009-04-01
Project End
2013-03-31
Budget Start
2011-04-01
Budget End
2013-03-31
Support Year
5
Fiscal Year
2011
Total Cost
$236,938
Indirect Cost
Name
Medical University of South Carolina
Department
Type
Schools of Dentistry
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Talwar, Sudha; House, Reniqua; Sundaramurthy, Santhanalakshmi et al. (2014) Inhibition of caspases protects mice from radiation-induced oral mucositis and abolishes the cleavage of RNA-binding protein HuR. J Biol Chem 289:3487-500
Talwar, Sudha; Balasubramanian, Sundaravadivel; Sundaramurthy, Santhanalakshmi et al. (2013) Overexpression of RNA-binding protein CELF1 prevents apoptosis and destabilizes pro-apoptotic mRNAs in oral cancer cells. RNA Biol 10:277-86
Ramachandran, Saraswathi; Palanisamy, Viswanathan (2012) Horizontal transfer of RNAs: exosomes as mediators of intercellular communication. Wiley Interdiscip Rev RNA 3:286-93
Palanisamy, V; Jakymiw, A; Van Tubergen, E A et al. (2012) Control of cytokine mRNA expression by RNA-binding proteins and microRNAs. J Dent Res 91:651-8
Yu, Hong; Sun, Yuhao; Haycraft, Courtney et al. (2011) MKP-1 regulates cytokine mRNA stability through selectively modulation subcellular translocation of AUF1. Cytokine 56:245-55
Sharma, Shivani; Gillespie, Boyd M; Palanisamy, Viswanathan et al. (2011) Quantitative nanostructural and single-molecule force spectroscopy biomolecular analysis of human-saliva-derived exosomes. Langmuir 27:14394-400
Talwar, Sudha; Jin, Junfei; Carroll, Brittany et al. (2011) Caspase-mediated cleavage of RNA-binding protein HuR regulates c-Myc protein expression after hypoxic stress. J Biol Chem 286:32333-43
Palanisamy, Viswanathan; Sharma, Shivani; Deshpande, Amit et al. (2010) Nanostructural and transcriptomic analyses of human saliva derived exosomes. PLoS One 5:e8577
Palanisamy, Viswanathan; Wong, David T (2010) Transcriptomic analyses of saliva. Methods Mol Biol 666:43-51
Sharma, Shivani; Rasool, Haider I; Palanisamy, Viswanathan et al. (2010) Structural-mechanical characterization of nanoparticle exosomes in human saliva, using correlative AFM, FESEM, and force spectroscopy. ACS Nano 4:1921-6