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MicroRNA and Cancer Drug Resistance

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MicroRNA in Development and in the Progression of Cancer

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Abstract

The last decade witnessed exponential growth in our understanding of the role of microRNAs (miRNAs) in cancer. In addition to a clearly defined role in cancer initiation and progression, miRNAs are now believed to determine sensitivity to therapy. The post-genomic era has seen rapid growth in our understanding of drug resistance mechanisms at the genomic level including genomic aberrations involving miRNA clusters and in the development of targeted therapies. Aberrant activity of a single miRNA can influence multiple signaling pathways associated with therapeutic response because it can target multiple proteins. Although it is difficult to pinpoint a single downstream effector of a miRNA, studies focusing on known oncogenes and tumor suppressors targeted by miRNA as well as advanced bioinformatics capabilities have enabled the discovery of integrated mRNA–miRNA–protein circuitry in cancer cells that govern multiple aspects of cancer including drug sensitivity. These studies have provided evidence for specific miRNAs targeting signaling molecules involved in drug transport, drug metabolism, synthesis of ligands for receptors, drug-induced DNA damage response and apoptotic pathways, and growth factor receptors/kinases/phosphatases that form the backbone of targeted therapies. Extensive knowledge of miRNA expression pattern and targets has allowed clinical translation of miRNAs as prognostic and predictive markers of therapies. miRNAs expressed in cancer cells govern signaling not only in cancer cells but also in neighboring cells and distant organs because they are incorporated into secretory microvesicles, remain stable in body fluids, and cross plasma membrane or cell–cell junctions. These properties of miRNAs have generated considerable interest in developing means to restore “normal miRNA patterns” in cancer through therapeutic approaches. Indeed, miRNA-based therapies are already in phase II clinical trial for hepatitis C infection, confirming feasibility of this approach. Therefore, miRNA or miRNA antagomir-based therapies are likely the next-revolutionary therapeutic approach to combat cancer.

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Authors and Affiliations

  1. Departments of Surgery, Indiana University School of Medicine, 46202, Indianapolis, IN, USA

    Daohong Chen & Harikrishna Nakshatri

  2. Biochemistry & Molecular Biology, Indiana University School of Medicine, C218E, 980 West Walnut St, Indianapolis, IN, 46202, USA

    Harikrishna Nakshatri

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  1. Daohong Chen
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Correspondence to Harikrishna Nakshatri .

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  1. National Cancer Institute Mouse Cancer Genetics Program, Frederick, Maryland, USA

    Shree Ram Singh

  2. UMDNJ-NJ Medical School, Newark, New Jersey, USA

    Pranela Rameshwar

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Chen, D., Nakshatri, H. (2014). MicroRNA and Cancer Drug Resistance. In: Singh, S., Rameshwar, P. (eds) MicroRNA in Development and in the Progression of Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4899-8065-6_16

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