Abstract
MicroRNAs (miRNAs) are ∼22 nucleotide non-coding RNA molecules that regulate gene expression post-transcriptionally. Although aberrant expression of miRNAs in various human cancers suggests a role for miRNAs in tumorigenesis, it remains largely unclear as to whether knockdown of a specific miRNA affects tumor growth. In this study, we profiled miRNA expression in matched normal breast tissue and breast tumor tissues by TaqMan real-time polymerase chain reaction miRNA array methods. Consistent with previous findings, we found that miR-21 was highly overexpressed in breast tumors compared to the matched normal breast tissues among 157 human miRNAs analysed. To better evaluate the role of miR-21 in tumorigenesis, we transfected breast cancer MCF-7 cells with anti-miR-21 oligonucleotides and found that anti-miR-21 suppressed both cell growth in vitro and tumor growth in the xenograft mouse model. Furthermore, this anti-miR-21-mediated cell growth inhibition was associated with increased apoptosis and decreased cell proliferation, which could be in part owing to downregulation of the antiapoptotic Bcl-2 in anti-miR-21-treated tumor cells. Together, these results suggest that miR-21 functions as an oncogene and modulates tumorigenesis through regulation of genes such as bcl-2 and thus, it may serve as a novel therapeutic target.
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Acknowledgements
We are grateful to CHTN and SIU tumor bank for providing patient specimens. We thank Rupinder Grewal and Heather Mizeur for cutting frozen tumor samples. This study was supported in part by Grants CA102630 from NCI and BC045418 from DOD.
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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).
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Si, ML., Zhu, S., Wu, H. et al. miR-21-mediated tumor growth. Oncogene 26, 2799–2803 (2007). https://doi.org/10.1038/sj.onc.1210083
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DOI: https://doi.org/10.1038/sj.onc.1210083
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