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Prostaglandin E2 promotes intestinal tumor growth via DNA methylation

Abstract

Although aberrant DNA methylation is considered to be one of the key ways by which tumor-suppressor and DNA-repair genes are silenced during tumor initiation and progression, the mechanisms underlying DNA methylation alterations in cancer remain unclear. Here we show that prostaglandin E2 (PGE2) silences certain tumor-suppressor and DNA-repair genes through DNA methylation to promote tumor growth. These findings uncover a previously unrecognized role for PGE2 in the promotion of tumor progression.

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Figure 1: PGE2 silences certain tumor-suppressor and DNA-repair genes by enhancing their promoter CGI methylation in human CRC cell lines.
Figure 2: PGE2 promotes intestinal tumor growth through the upregulation of CGI methylation in ApcMin/+ mice.

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Acknowledgements

We thank D. Menter and P. Yang for their suggestions and help in the measurement of PGE2. This work is supported, in part, by the US National Institutes of Health MERIT award grants R37 DK47297, RO1 DK62112, NCI P01 CA77839 and CPRIT RP100960. We also thank the National Colorectal Cancer Research Alliance (NCCRA) for its generous support (R.N.D.) and a cancer prevention fellowship (D.X.) supported by the National Cancer Institute grant R25T CA57730 (principal investigator, S. Chang).

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Contributions

R.N.D., D.W. and D.X. designed this research project. D.X. performed most of the experiments. S.-H.K. contributed to establish the DNMT1 and DNMT3B knockdown stable cell lines, and H.K. conducted the DNA methylation analysis for the human tissues samples. D.X. and D.W. conducted the data analyses. D.W. wrote the manuscript with help from D.X. R.N.D. supervised the project.

Corresponding author

Correspondence to Raymond N DuBois.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–5, Supplementary Tables 1 and 2, Supplementary Discussion and Supplementary Methods (PDF 2314 kb)

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Xia, D., Wang, D., Kim, SH. et al. Prostaglandin E2 promotes intestinal tumor growth via DNA methylation. Nat Med 18, 224–226 (2012). https://doi.org/10.1038/nm.2608

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