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MicroRNAs play a central role in molecular dysfunctions linking inflammation with cancer

Authors

  • Esmerina Tili,

    1. Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, Comprehensive Cancer Center, Columbus, OH, USA
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  • Jean-Jacques Michaille,

    1. Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, Comprehensive Cancer Center, Columbus, OH, USA
    2. LBMN-INSERM U866, Université de Bourgogne, Faculté Gabriel, Dijon, France
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  • Carlo M. Croce

    Corresponding author
    • Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, Comprehensive Cancer Center, Columbus, OH, USA
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Correspondence to:

Carlo Maria Croce

Ohio State University

Department of Molecular Virology, Immunology and Medical Genetics

Biomedical Research Tower

460 W. 12th Avenue

Columbus, OH 43210, USA

Tel.: +1 614 292 3063

Fax: +1 614 292 3558

e-mail: carlo.croce@osumc.edu

Summary

It is now largely admitted that a pro-inflammatory environment may curtail anti-tumor immunity and favor cancer initiation and progression. The discovery that small non-coding regulatory RNAs, namely microRNAs (miRNAs), regulate all aspects of cell proliferation, differentiation, and function has shed a new light on regulatory mechanisms linking inflammation and cancer. Thus, miRNAs such as miR-21, miR-125b, miR-155, miR-196, and miR-210 that are critical for the immune response or hypoxia are often overexpressed in cancers and leukemias. Given the high number of their target transcripts, their deregulation may have a number of deleterious consequences, depending on the cellular context. In this review, we focus on how the factors encoded by transcripts targeted by these five miRNAs, be they transcription factors, tumor-suppressors, or regulators of different signaling pathways, can deregulate the immune response and favor pro-tumor immunity. Furthermore, we expose how the misdirected action of the main regulators of these miRNAs, such as nuclear factor κB (NF-κB), activator protein-1 (AP-1), and signal transduction and activators of transcription (STAT) transcription factors, or AKT and transforming growth factor β (TGFβ) signaling pathways, can contribute to decrease anti-tumor immunity and enhance cell proliferation and oncogenesis. We conclude by briefly discussing about how these discoveries may possibly lead to the development of new miRNA-based cancer therapies.

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