Research Papers:

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

Jaeyun Jung, Chanjoo Yeom, Yeon-Sook Choi, Sinae Kim, EunJi Lee, Min Ji Park, Sang Wook Kang, Sung Bae Kim and Suhwan Chang _

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Oncotarget. 2015; 6:20370-20387. https://doi.org/10.18632/oncotarget.4827

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Jaeyun Jung1, Chanjoo Yeom2, Yeon-Sook Choi2, Sinae Kim1, EunJi Lee1, Min Ji Park1, Sang Wook Kang1, Sung Bae Kim1,2, Suhwan Chang1,2

1Department of Biomedical Sciences, University of Ulsan School of Medicine, Seoul 138-736, Korea

2Asan Medical Center, Seoul 138-736, Korea

Correspondence to:

Suhwan Chang, e-mail: [email protected]

Keywords: oncogenic microRNA, miRNA inhibitor, miRNA sponge, breast cancer, pancreatic cancer

Received: September 12, 2014     Accepted: July 11, 2015     Published: July 30, 2015


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.

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