Abstract
The transcription factor glioma-associated antigen-1 (Gli-1) mediates activation of the sonic hedgehog (Shh) pathway, a process that precedes the transformation of tissue stem cells into cancerous stem cells and that is involved in early and late epithelial tumorigenesis. Hypothesizing that targeting the 3′-untranslated region (3′-UTR) of Gli-1 mRNA would effectively inhibit epithelial tumor cell proliferation, we evaluated several complementary miRNA molecules for their ability to do so. The synthetic miRNAs and corresponding duplex/small temporal RNAs were introduced as 3-nucleotide (nt) loops into GU-rich portions of the 3′UTR Gli-1 sequence. One particular miRNA (miRNA Gli-1-3548) and its corresponding duplex (Duplex 3548) significantly inhibited proliferation of Gli-1+ ovarian (SK-OV-3) and pancreatic (MiaPaCa-2) tumor cells by delaying cell division and activating late apoptosis in MiaPaCa-2 cells. Here, we describe the design of effective miRNA sequences and their applications as anti-gene agents.
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Acknowledgements
This work has been supported in part by the Topfer Pancreatic Cancer Research Fund (DZC, NT), Grant DOD-01-1-299 (CGI, NT), and grant from the 21st Century COE program from the Kurume University (NT, TM).
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Tsuda, N., Mine, T., Ioannides, C., Chang, D. (2009). Synthetic microRNA Targeting Glioma-associated Antigen-1 Protein. In: Sioud, M. (eds) siRNA and miRNA Gene Silencing. Methods in Molecular Biology, vol 487. Humana Press. https://doi.org/10.1007/978-1-60327-547-7_21
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DOI: https://doi.org/10.1007/978-1-60327-547-7_21
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