MicroRNAs in body fluids—the mix of hormones and biomarkers

Abstract

Since the discovery of microRNAs (miRNAs), the study of these small noncoding RNAs has steadily increased and more than 10,000 papers have already been published. The great interest in miRNAs reflects their central role in gene-expression regulation and the implication of miRNA-specific aberrant expression in the pathogenesis of cancer, cardiac, immune-related and other diseases. Another avenue of current research is the study of circulating miRNAs in serum, plasma, and other body fluids—miRNAs may act not only within cells, but also at other sites within the body. The presence of miRNAs in body fluids may represent a gold mine of noninvasive biomarkers in cancer. Since deregulated miRNA expression is an early event in tumorigenesis, measuring circulating miRNA levels may also be useful for early cancer detection, which can contribute greatly to the success of treatment. In this Review, we discuss the role of fluid-expressed miRNAs as reliable cancer biomarkers and treatment-response predictors as well as potential new patient selection criteria for clinical trials. In addition, we explore the concept that miRNAs could function as hormones.

Key Points

  • A single microRNA (miRNA) can target and regulate hundreds or thousands of mRNAs; aberrant miRNA expression is involved in the initiation of many diseases, including cancer

  • MiRNAs are potentially useful as biomarkers in cancer diagnosis, prognosis and response to treatment owing to the unique expression profile of each tumor and limited complex transcriptional and translational modifications

  • The discovery of miRNAs in body fluids opens up the possibility of using them as non-invasive biomarkers in cancer detection and as predictors of therapy response in clinical trials

  • Standardized methods with well-established parameters for miRNA detection are necessary to indicate cancer stage, response to treatment, outcome and cancer recurrence

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Figure 1: MiRNA biogenesis in the cell.
Figure 2: A miRNA can function dually as both an oncogene and tumor-suppressor gene depending on the cancer type and cellular context.
Figure 3: Biogenesis and mechanism of action of circulating miRNAs.

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Acknowledgements

G. A. Calin is supported as a Fellow at The University of Texas MD Anderson Research Trust, as a University of Texas System Regents Research Scholar and by the CLL Global Research Foundation. Work in G. A. Calin's laboratory is supported in part by the National Institutes of Health, a Department of Defense Breast Cancer Idea Award, Developmental Research Awards in MD Anderson's Breast Cancer, Ovarian Cancer, Brain Cancer, Multiple Myeloma and Leukemia SPOREs, a CTT/3I-TD grant, a 2009 Seena Magowitz–Pancreatic Cancer Action Network AACR Pilot Grant, and MD Anderson's Cancer Center Support Grant CA016672 and the Arnold Foundation. This work was also supported, in part, by U54 CA151668. We would like to thank Maude Veech (MD Anderson Cancer Center) for help with the editing of this manuscript. We apologize to all colleagues whose work was not cited because of space limitations. C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape, LLC-accredited continuing medical education activity associated with this article.

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M. A. Cortez and G. A. Calin devised, wrote and edited the article, J. Ferdin contributed to writing and C. Bueso-Ramos, G. Lopez-Berestein, and A. K. Sood contributed substantially to the content of the article through in-depth discussions and editing the manuscript.

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Correspondence to George A. Calin.

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Cortez, M., Bueso-Ramos, C., Ferdin, J. et al. MicroRNAs in body fluids—the mix of hormones and biomarkers. Nat Rev Clin Oncol 8, 467–477 (2011). https://doi.org/10.1038/nrclinonc.2011.76

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