Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92 (original) (raw)

• Short Communication
• Published: 26 March 2007
• T Takeuchi1 na1,
• E Nishikawa1 na1,
• K Yanagisawa1,
• Y Hayashita3,
• H Ebi1,
• H Yamada1,2,
• M Suzuki1,
• M Nagino2,
• Y Nimura2,
• H Osada3 &
• …
• T Takahashi1

Oncogene volume 26, pages 6099–6105 (2007)Cite this article

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Abstract

Amplification and overexpression of the miR-17-92 microRNAs (miRNA) cluster at 13q31.3 has recently reported, with pointers to functional involvement in the development of B-cell lymphomas and lung cancers. In the present study, we show that inhibition of miR-17-5p and miR-20a with antisense oligonucleotides (ONs) can induce apoptosis selectively in lung cancer cells overexpressing miR-17-92, suggesting the possibility of ‘OncomiR addiction’ to expression of these miRNAs in a subset of lung cancers. In marked contrast, antisense ONs against miR-18a and miR-19a did not exhibit such inhibitory effects, whereas inhibition of miR-92-1 resulted in only modest reduction of cell growth, showing significant distinctions among miRNAs of the miR-17-92 cluster in terms of their roles in cancer cell growth. During the course of this study, we also found that enforced expression of a genomic region, termed C2, residing 3′ to miR-17-92 in the intron 3 of C13orf25 led to marked growth inhibition in association with double stranded RNA-dependent protein kinase activation. Finally, this study also revealed that the vast majority of C13orf25 transcripts are detected as Drosha-processed cleavage products on Northern blot analysis and that a novel polyadenylation site is present 3′ to the miR-17-92 cluster and 5′ to the C2 region. Taken together, the present findings contribute towards better understanding of the oncogenic roles of miR-17-92, which might ultimately lead to the future translation into clinical applications.

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Acknowledgements

We thank Dr Yoshitaka Sekido at Aichi Cancer Center for his warm support during the course of this study. This work was financially supported in part by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan and a Grain-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science.

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Author notes

1. H Matsubara, T Takeuchi and E Nishikawa: These authors contributed equally to this work.

Authors and Affiliations

1. Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan,
   H Matsubara, T Takeuchi, E Nishikawa, K Yanagisawa, H Ebi, H Yamada, M Suzuki & T Takahashi
2. Department of Surgical Oncology, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan,
   H Matsubara, H Yamada, M Nagino & Y Nimura
3. Division of Molecular Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan
   Y Hayashita & H Osada

Authors

1. H Matsubara
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2. T Takeuchi
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3. E Nishikawa
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4. K Yanagisawa
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5. Y Hayashita
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6. H Ebi
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7. H Yamada
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8. M Suzuki
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9. M Nagino
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10. Y Nimura
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11. H Osada
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12. T Takahashi
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Corresponding author

Correspondence toT Takahashi.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Matsubara, H., Takeuchi, T., Nishikawa, E. et al. Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92.Oncogene 26, 6099–6105 (2007). https://doi.org/10.1038/sj.onc.1210425

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• Received: 06 December 2006
• Revised: 06 February 2007
• Accepted: 08 February 2007
• Published: 26 March 2007
• Issue Date: 06 September 2007
• DOI: https://doi.org/10.1038/sj.onc.1210425

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