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 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.
Department of Biomedical Sciences, University of Ulsan School of Medicine, Seoul 138-736, Korea.
Jaeyun
J
Jung
Asan Medical Center, Seoul 138-736, Korea.
Chanjoo
C
Yeom
Asan Medical Center, Seoul 138-736, Korea.
Yeon-Sook
YS
Choi
Department of Biomedical Sciences, University of Ulsan School of Medicine, Seoul 138-736, Korea.
Sinae
S
Kim
Department of Biomedical Sciences, University of Ulsan School of Medicine, Seoul 138-736, Korea.
EunJi
E
Lee
Department of Biomedical Sciences, University of Ulsan School of Medicine, Seoul 138-736, Korea.
Min Ji
MJ
Park
Department of Biomedical Sciences, University of Ulsan School of Medicine, Seoul 138-736, Korea.
Sang Wook
SW
Kang
Department of Biomedical Sciences, University of Ulsan School of Medicine, Seoul 138-736, Korea.|Asan Medical Center, Seoul 138-736, Korea.
Sung Bae
SB
Kim
Department of Biomedical Sciences, University of Ulsan School of Medicine, Seoul 138-736, Korea.|Asan Medical Center, Seoul 138-736, Korea.
Suhwan
S
Chang
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics*; D011161:Porifera / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection
D035683:MicroRNAs
breast cancer; miRNA inhibitor; miRNA sponge; oncogenic microRNA; pancreatic cancer