Date of Award

5-2021

Degree Name

Master of Science

Department

Chemistry

First Advisor

Dr. Kelly Teske

Second Advisor

Dr. David Huffman

Third Advisor

Dr. Pamela Hoppe

Keywords

MicroRNA-31, inhibitors, high-throughput screening, assay development, colorectal cancer

Access Setting

Masters Thesis-Open Access

Abstract

Dysregulated expression of miRNAs has been linked to numerous cancers. On the other hand, miRNAs are potential drug targets due to the ability of their precursor molecules to fold into ligand binding structures. Small-molecule modulators of miRNAs offers opportunity for the development of new therapeutic agents and tools to further probe the mechanisms of miRNA functions. To facilitate the identification of miRNA modulators, the appropriate screening systems are needed, which would be adaptable for high-throughput applications, and allow for quantitative measurements. In this text, we present a molecular beacon-based assay to identify molecules that inhibit miRNA-31 processing by Dicer and a cell-based luciferase assay to screen for small-molecules that inhibit miRNA-31 expression in colorectal cancer cells. Our goal was to explore the potential of these assays for use in high throughput experiments to facilitate discovery of new inhibitors of miRNA-31 as well as to enable structure activity relationship (SAR) studies with the potential drug compounds. We discuss the development of these assays as screening methods to identify small molecule miRNA-31 inhibitors. These assays can also be adapted for studies of other miRNAs.

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