Simultaneous inhibition of multiple oncogenic miRNAs by a multi-potent microRNA sponge

The roles of oncogenic miRNAs are widely recognized in many cancers. Inhibition of single miRNA using antagomiR can efficiently knock-down a specific miRNA. However, the effect is transient and often results in subtle phenotype, as there are other miRNAs contribute to tumorigenesis. Here we report a...

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Bibliographic Details
Published in:Oncotarget 2015-08, Vol.6 (24), p.20370-20387
Main Authors: Jung, Jaeyun, Yeom, Chanjoo, Choi, Yeon-Sook, Kim, Sinae, Lee, EunJi, Park, Min Ji, Kang, Sang Wook, Kim, Sung Bae, Chang, Suhwan
Format: Article
Language:English
Subjects:
Animals
Breast Neoplasms - genetics
Cell Line, Tumor
Cell Movement
Cell Proliferation
Female
Gene Expression Regulation, Neoplastic
Humans
MicroRNAs - genetics
Pancreatic Neoplasms - genetics
Porifera - genetics
Porifera - metabolism
Research Paper
Transfection
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Summary:The roles of oncogenic miRNAs are widely recognized in many cancers. Inhibition of single miRNA using antagomiR can efficiently knock-down a specific miRNA. However, the effect is transient and often results in subtle phenotype, as there are other miRNAs contribute to tumorigenesis. Here we report a multi-potent miRNA sponge inhibiting multiple miRNAs simultaneously. As a model system, we targeted miR-21, miR-155 and miR-221/222, known as oncogenic miRNAs in multiple tumors including breast and pancreatic cancers. To achieve efficient knockdown, we generated perfect and bulged-matched miRNA binding sites (MBS) and introduced multiple copies of MBS, ranging from one to five, in the multi-potent miRNA sponge. Luciferase reporter assay showed the multi-potent miRNA sponge efficiently inhibited 4 miRNAs in breast and pancreatic cancer cells. Furthermore, a stable and inducible version of the multi-potent miRNA sponge cell line showed the miRNA sponge efficiently reduces the level of 4 target miRNAs and increase target protein level of these oncogenic miRNAs. Finally, we showed the miRNA sponge sensitize cells to cancer drug and attenuate cell migratory activity. Altogether, our study demonstrates the multi-potent miRNA sponge is a useful tool to examine the functional impact of simultaneous inhibition of multiple miRNAs and proposes a therapeutic potential.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.4827