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Regression of murine lung tumors by the let-7 microRNA

Oncogene volume 29, pages 1580–1587 (2010)Cite this article

Abstract

MicroRNAs (miRNAs) have recently emerged as an important new class of cellular regulators that control various cellular processes and are implicated in human diseases, including cancer. Here, we show that loss of let-7 function enhances lung tumor formation in vivo, strongly supporting the hypothesis that let-7 is a tumor suppressor. Moreover, we report that exogenous delivery of let-7 to established tumors in mouse models of non-small-cell lung cancer (NSCLC) significantly reduces the tumor burden. These results demonstrate the therapeutic potential of let-7 in NSCLC and point to miRNA replacement therapy as a promising approach in cancer treatment.

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Acknowledgements

We acknowledge Xianping Liang for help with animal husbandry and genotyping, and Paul Lebourgeois for histopathological analyses. PT was supported by an NIH NRSA postdoctoral fellowship (F32CA130376). PM was supported by a postdoctoral fellowship from the Ministry of Education and Science of Spain (MEC) and from the Hope Funds for Cancer Research. JBW was supported by the ASTRO Junior Faculty Career Research Training Award. FJS and JBW were supported by grants from the NIH (CA131301-01A1) and from the Connecticut Department of Public Health (RFP no. 2006-0913).

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Author notes

  1. P Trang and P P Medina: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA

    P Trang, P P Medina & F J Slack

  2. Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA

    P Trang & J B Weidhaas

  3. Mirna Therapeutics Inc. (a subsidiary of Asuragen Inc.), Austin, TX, USA

    J F Wiggins, L Ruffino, K Kelnar, M Omotola, D Brown & A G Bader

  4. Department of Pathology, Yale University School of Medicine, New Haven, CT, USA

    R Homer

  5. Department of Pathology and Laboratory Medicine Service, VA Connecticut Healthcare System, West Haven, CT, USA

    R Homer

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  1. P Trang
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  2. P P Medina
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  3. J F Wiggins
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  4. L Ruffino
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  5. K Kelnar
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  6. M Omotola
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  7. R Homer
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  8. D Brown
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  9. A G Bader
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  11. F J Slack
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Corresponding authors

Correspondence to A G Bader, J B Weidhaas or F J Slack.

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

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Trang, P., Medina, P., Wiggins, J. et al. Regression of murine lung tumors by the let-7 microRNA. Oncogene 29, 1580–1587 (2010). https://doi.org/10.1038/onc.2009.445

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