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MicroRNA-339 and microRNA-556 regulate Klotho expression in vitro

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Abstract

Klotho is an anti-aging protein with direct effects on life-span in mice. Klotho functions to regulate pathways classically associated with longevity including insulin/IGF1 and Wnt signaling. Decreased Klotho protein expression is observed throughout the body during the normal aging process. While increased methylation of the Klotho promoter is reported, other epigenetic mechanisms could contribute to age-related downregulation of Klotho expression, including microRNA-mediated regulation. Following in silico identification of potential microRNA binding sites within the Klotho 3′ untranslated region, reporter assays reveal regulation by microRNA-339, microRNA-556, and, to a lesser extent, microRNA-10 and microRNA-199. MicroRNA-339 and microRNA-556 were further found to directly decrease Klotho protein expression indicating that, if upregulated in aging tissue, these microRNA could play a role in age-related downregulation of Klotho messenger RNA. These microRNAs are differentially regulated in cancer cells compared to normal cells and may imply a role for microRNA-mediated regulation of Klotho in cancer.

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Acknowledgments

This work was funded by National Institutes of Health/National Institute on Aging R00 AG034989 (GDK).

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Authors and Affiliations

  1. Department of Neurobiology, University of Alabama at Birmingham, 1825 University Blvd, Shelby Building 913, Birmingham, AL, 35294, USA

    Stephen J. Mehi, Astha Maltare & Gwendalyn D. King

  2. Department of Biochemistry, Boston University School of Medicine, 72 East Concord Street K304, Boston, MA, 02118, USA

    Carmela R. Abraham

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  1. Stephen J. Mehi
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  2. Astha Maltare
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  3. Carmela R. Abraham
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  4. Gwendalyn D. King
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Correspondence to Gwendalyn D. King.

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Mehi, S.J., Maltare, A., Abraham, C.R. et al. MicroRNA-339 and microRNA-556 regulate Klotho expression in vitro. AGE 36, 141–149 (2014). https://doi.org/10.1007/s11357-013-9555-6

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