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The proto-oncogene Pim-1 is a target of miR-33a

Oncogene volume 31, pages 918–928 (2012)Cite this article

Abstract

The constitutively active serine/threonine kinase Pim-1 is upregulated in different cancer types, mainly based on the action of several interleukines and growth factors at the transcriptional level. So far, a regulation of oncogenic Pim-1 by microRNAs (miRNAs) has not been reported. Here, we newly establish miR-33a as a miRNA with potential tumor suppressor activity, acting through inhibition of Pim-1. A screen for miRNA expression in K562 lymphoma, LS174T colon carcinoma and several other cell lines revealed generally low endogenous miR-33a levels relative to other miRNAs. Transfection of K562 and LS174T cells with a miR-33a mimic reduced Pim-1 levels substantially. In contrast, the cell-cycle regulator cyclin-dependent kinase 6 predicted to be a conserved miR-33a target, was not downregulated by the miR-33a mimic. Seed mutagenesis of the Pim-1 3′-untranslated region in a luciferase reporter construct and in a Pim-1 cDNA expressed in Pim-1-deficient Skov-3 cells demonstrated specific and direct downregulation of Pim-1 by the miR-33a mimic. The persistence of this effect was comparable to that of a small interfering RNA-mediated knockdown of Pim-1, resulting in decelerated cell proliferation. In conclusion, we demonstrate the potential of miR-33a to act as a tumor suppressor miRNA, which suggests miR-33a replacement therapy through delivery of miR mimics as a novel therapeutic strategy.

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Acknowledgements

We thank Robert Prinz, Dorothee Hartmann, Dennis Streng, Meike Thomas and Heide Marika Genau for technical support. This study was supported by the Fritz Thyssen Stiftung (reference no. 10.06.1.186 to AG and RKH), the Deutsche Krebshilfe (reference no. 109260 to AG, RKH and AA, and reference no. 106992 to AA) and DFG Forschergruppe Nanohale (AI 24/6-1).

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  1. Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, Philipps-University Marburg, Marburg, Germany

    M Thomas, K Lange-Grünweller, A Grünweller & R K Hartmann

  2. Institute of Pharmacology, Faculty of Medicine, Philipps-University Marburg, Marburg, Germany

    U Weirauch, D Gutsch & A Aigner

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  1. M Thomas
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Correspondence to A Grünweller or R K Hartmann.

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Thomas, M., Lange-Grünweller, K., Weirauch, U. et al. The proto-oncogene Pim-1 is a target of miR-33a. Oncogene 31, 918–928 (2012). https://doi.org/10.1038/onc.2011.278

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