Abstract
miRNAs are small non-coding RNAs that finely regulate gene expression in cells. Alterations in miRNA expression have been associated with development of cancer, and miRNAs are now being investigated as biomarkers for cancer as well as other diseases. Recently, miRNAs have been found outside cells in body fluids. Extracellular miRNAs exist in different forms – associated with Ago2 proteins, loaded into extracellular vesicles (exosomes, microvesicles, or apoptotic bodies) or into high density lipoprotein particles. These extracellular miRNAs are probably products of distinct cellular processes, and might therefore play different roles. However, their functions in vivo are currently unknown. In spite of this, they are considered as promising, non-invasive diagnostic, and prognostic tools. Prostate cancer is the most common cancer in men in the Western world, but the currently used biomarker (prostate specific antigen) has low specificity. Therefore, novel biomarkers are highly needed. In this review we will discuss possible biological functions of extracellular miRNAs, as well as the potential use of miRNAs from extracellular vesicles as biomarkers for prostate cancer.
Highlights
Exosomal miRNAs as biomarkers for prostate cancerReviewed by: Francesca Fanini, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Italy Alessio Paone, Ohio State University, USA
INTRODUCTION miRNAs are 19–23 nucleotides long non-coding RNAs that play important gene-regulatory roles (Carrington and Ambros, 2003; Bartel, 2004). These small RNAs downregulate gene expression through incorporation into the RNA-induced silencing complex (RISC), which binds to partially complementary sites mainly in the 3 untranslated region (3 UTR) of their mRNA targets (Bartel, 2004)
Among the aforementioned miRNAs suggested as biomarker candidates in clinical studies, we identified 36 in exosomes from PC-3 cells (Hessvik et al, 2012)
Summary
Reviewed by: Francesca Fanini, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Italy Alessio Paone, Ohio State University, USA. FORMS OF EXTRACELLULAR miRNAs Recently, miRNAs have been identified in the medium from cultured cells (Valadi et al, 2007) and in many body fluids like blood (Chim et al, 2008; Lawrie et al, 2008), urine (Hanke et al, 2010), saliva (Park et al, 2009), breast milk (Kosaka et al, 2010b; Weber et al, 2010), and seminal plasma (Weber et al, 2010) Some of these miRNAs appear in extracellular stable forms, which render them interesting as biomarkers for cancer and other diseases. Some reports have shown that most of the extracellular miRNAs www.frontiersin.org
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