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MiR-27b targets PPARγ to inhibit growth, tumor progression and the inflammatory response in neuroblastoma cells

Oncogene volume 31, pages 3818–3825 (2012)Cite this article

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Abstract

The peroxisome proliferators-activated receptor (PPAR)γ pathway is involved in cancer, but it appears to have both tumor suppressor and oncogenic functions. In neuroblastoma cells, miR-27b targets the 3′ untranslated region of PPARγ and inhibits its mRNA and protein expression. miR-27b overexpression or PPARγ inhibition blocks cell growth in vitro and tumor growth in mouse xenografts. PPARγ activates expression of the pH regulator NHE1, which is associated with tumor progression. Lastly, miR-27b through PPARγ regulates nuclear factor-κB activity and transcription of inflammatory target genes. Thus, in neuroblastoma, miR-27b functions as a tumor suppressor by inhibiting the tumor-promoting function of PPARγ, which triggers an increased inflammatory response. In contrast, in breast cancer cells, PPARγ inhibits NHE1 expression and the inflammatory response, and it functions as a tumor suppressor. We suggest that the ability of PPARγ to promote or suppress tumor formation is linked to cell type-specific differences in regulation of NHE1 and other target genes.

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Acknowledgements

This work was supported by start-up funds to DI from the Dana Farber Cancer Institute and by a research grant to KS from the National Institutes of Health (CA 107486).

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Authors and Affiliations

  1. Department Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA

    J-J Lee, D Iliopoulos & K Struhl

  2. Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA

    A Drakaki

  3. Department Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA, USA

    D Iliopoulos

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  1. J-J Lee
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Correspondence to K Struhl.

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Lee, JJ., Drakaki, A., Iliopoulos, D. et al. MiR-27b targets PPARγ to inhibit growth, tumor progression and the inflammatory response in neuroblastoma cells. Oncogene 31, 3818–3825 (2012). https://doi.org/10.1038/onc.2011.543

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