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Title:Enhancement of Dicer as a personalized anticancer strategy
Author(s):Knowlton, Aaron
Advisor(s):Hergenrother, Paul J.
Department / Program:Biochemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
transactivating response RNA-binding protein (TRBP)
transactivating response RNA-binding protein 2 (tarbp2)
micro ribonucleic acid (miRNA)
Hereditary nonpolyposis colorectal cancer (HNPCC)
Malachite green
Abstract:Normal miRNA production is essential for regulating protein expression and cellular fate. Misregulation of miRNA production is emerging as a key factor in the development of many disease states, including most forms cancer. A global downregulation of miRNA processing is common among cancers and has been shown to drive tumorogenesis. This global downregulation of miRNA biogenesis is caused by the disruption of key enzymes in the miRNA biogenesis pathway like Dicer, TAR RNA-binding protein (TRBP) and Drosha. Herein, the enhancement of miRNA processing as a therapeutic strategy is explored. Developing small molecule or peptide based therapeutics that mimic TRBP, an endogenous activator of Dicer, to enhance miRNA processing in cancers with reduced miRNA production may lead to safe and effective treatments for a number of cancer patients. Identification of direct activators of Dicer will be explored using in vitro kinetic assays with fluorescent probes. Expression of Dicer, TRBP and a peptide-mapping library of TRBP are also described. Since miRNA biogenesis is such a critical pathway in tumorogenesis, activation of this pathway may prove to be an effective target in the battle against cancer.
Issue Date:2012-09-18
Rights Information:Copyright 2012 Aaron Knowlton
Date Available in IDEALS:2012-09-18
Date Deposited:2012-08

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