Cancer and Metastasis Reviews

, Volume 30, Issue 3–4, pp 419–435 | Cite as

MicroRNA and AU-rich element regulation of prostaglandin synthesis

  • Ashleigh E. Moore
  • Lisa E. Young
  • Dan A. Dixon
Article

Abstract

Many lines of evidence demonstrate that prostaglandins play an important role in cancer, and enhanced synthesis of prostaglandin E2 (PGE2) is often observed in various human malignancies often associated with poor prognosis. PGE2 synthesis is initiated with the release of arachidonic acid by phospholipase enzymes, where it is then converted into the intermediate prostaglandin prostaglandin H2 (PGH2) by members of the cyclooxygenase family. The synthesis of PGE2 from PGH2 is facilitated by three different PGE synthases, and functional PGE2 can promote tumor growth by binding to four EP receptors to activate signaling pathways that control cell proliferation, migration, apoptosis, and angiogenesis. An integral method of controlling gene expression is by posttranscriptional mechanisms that regulate mRNA stability and protein translation. Messenger RNA regulatory elements typically reside within the 3′ untranslated region (3′UTR) of the transcript and play a critical role in targeting specific mRNAs for posttranscriptional regulation through microRNA (miRNA) binding and adenylate- and uridylate-rich element RNA-binding proteins. In this review, we highlight the current advances in our understanding of the impact these RNA sequence elements have upon regulating PGE2 levels. We also identify various RNA sequence elements consistently observed within the 3′UTRs of the genes involved in the PGE2 pathway, indicating these binding sites for miRNAs and RNA-binding proteins to be central regulators of PGE2 synthesis and function. These findings may provide a rationale for the development of new therapeutic approaches to control tumor growth and metastasis promoted by elevated PGE2 levels.

Keywords

Cyclooxygenase Prostaglandin MicroRNA Posttranscriptional regulation AU-rich element 

Notes

Acknowledgments

The authors were funded by grants from the National Institutes of Health (R01CA134609) and American Cancer Society (RSG-06-122-01-CNE). We apologize to our colleagues for not being able to refer all primary work due to space limitations.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Ashleigh E. Moore
    • 1
  • Lisa E. Young
    • 2
  • Dan A. Dixon
    • 1
  1. 1.Department of Biological Sciences and Center for Colon Cancer ResearchUniversity of South CarolinaColumbiaUSA
  2. 2.Novartis Institutes for Biomedical Research, RNAi TherapeuticsCambridgeUSA

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