Enhancement of Dicer as a personalized anticancer strategy

Knowlton, Aaron

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https://hdl.handle.net/2142/34568 Copy

Description

Title

Enhancement of Dicer as a personalized anticancer strategy

Author(s)

Knowlton, Aaron

Issue Date

2012-09-18T21:25:58Z

Director of Research (if dissertation) or Advisor (if thesis)

Hergenrother, Paul J.

Department of Study

Biochemistry

Discipline

Biochemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

M.S.

Degree Level

Thesis

Keyword(s)

• Dicer
• transactivating response RNA-binding protein (TRBP)
• Dicer1
• transactivating response RNA-binding protein 2 (tarbp2)
• micro ribonucleic acid (miRNA)
• cancer
• Hereditary nonpolyposis colorectal cancer (HNPCC)
• aptamer
• 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.

Graduation Semester

2012-08

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http://hdl.handle.net/2142/34568

Copyright and License Information

Copyright 2012 Aaron Knowlton

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