Applications of Extracellular RNAs in Oncology
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CURRENT OPINION
Applications of Extracellular RNAs in Oncology Jonathan R. Thompson1 • Jing Zhu2 • Deepak Kilari1 • Liang Wang2
Ó Springer International Publishing Switzerland 2016
Abstract Extracellular RNAs consist of coding and noncoding transcripts released from all cell types, which are involved in multiple cellular processes, predominantly through regulation of gene expression. Recent advances have helped us better understand the functions of these molecules, particularly microRNAs (miRNAs). Numerous pre-clinical and human studies have demonstrated that miRNAs are dysregulated in cancer and contribute to tumorigenesis and metastasis. miRNA profiling has extensively been evaluated as a non-invasive method for cancer diagnosis, prognostication, and assessment of response to cancer therapies. Broader applications for miRNAs in these settings are currently under active development. Investigators have also moved miRNAs into the realm of cancer therapy. miRNA antagonists targeting miRNAs that silence tumor suppressor genes have shown promising pre-clinical activity. Alternatively, miRNA mimics that silence oncogenes are also under active investigation. These miRNA-based cancer therapies are in early development, but represent novel strategies for clinical management of human cancer.
& Liang Wang [email protected] 1
Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA
2
Department of Pathology and MCW Cancer Center, TBRC-C4970, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
Key Points Extracellular RNAs, in particular miRNAs, are involved in various cellular processes and play a key role in gene regulation. Because of their stability in circulation and key regulatory role, extracellular RNAs are believed to be promising biomarkers and therapeutic targets in clinical management of human cancers.
1 Introduction Extracellular ribonucleic acids (exRNAs) consist of coding and non-coding RNA transcripts that are released from the cell of their transcription and predominantly stored in small (30–100 nm), cell membrane-derived vesicles called exosomes. A variety of exosomal RNAs have been described, including messenger RNA (mRNA), transfer RNA (tRNA), microRNA (miRNA), piwi-interacting RNA (piRNA), small nucleolar RNA (snoRNA), and long non-coding RNA (lncRNA). Exosomal RNAs are integral in gene expression, cell signaling, proliferation, angiogenesis, apoptosis, and development, and are known to be frequently dysregulated in cancer [1–6]. Storage within exosomes allows exRNAs to avoid degradation by extracellular enzymes [7]. As a result, exRNAs are not only remarkably stable in serum, plasma, and urine, but can also be easily obtained from patients, thereby making them excellent candidates to serve as biomarkers for human diseases, particularly cancer. Cancer is the second leading cause of death worldwide. Across various cancer subtypes, there are only a few
J. R. Thompson et al.
reliable biomarkers. Tissue-based assa
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