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Discovery of novel ligands for breast cancer-related microRNA precursors
Tumor Cell Biology V
The recent advances in the discovery and analysis of small non-coding RNAs especially microRNAs (miRNAs), are expected to have significant influence on cancer research. A recent study showed that breast cancer cells exhibit characteristic miRNA expression patterns which may provide important diagnostic information as well as potential targets for therapy. The objective of the proposed pilot research is to use combinatorial tools such as phage display and DNA display to select peptides and proteins that specifically bind to miRNA precursors that are aberrantly overexpressed in breast cancer cells. Such specific ligands for miRNAs may lead to several important potential applications. 1) The ligands may be used as elements in miRNA precursor sensors. 2) The ligands may function as inhibitors of miRNA maturation.
Recently, a new class of biomolecules called microRNAs (miRNAs) have been discovered and their important roles in biology and pathogenesis including cancer are being revealed. MiRNAs are derived from longer precursors that are processed by a number of enzymes and protein factors into small RNAs consisting of about 22 ribonucleotide monomers. The mature miRNAs function by inhibiting the production of proteins from messenger RNAs that contain complementary sequences. Recent research efforts have shown that breast cancer cells exhibit abnormal expression of certain miRNAs. The goal of this proposal is to develop novel molecular tools that can specifically recognize and bind to the miRNA precursors that are abnormally overexpressed in breast cancer cells. The peptide and protein ligands that will be discovered through this proposal are expected to enable the breast cancer research community to further dissect the biological roles of miRNAs in breast cancer, to develop new diagnostic systems, and to develop novel therapeutic strategies.