Abstract
Long non-coding RNAs (lncRNAs) comprise a diverse class of RNA transcripts >200 nucleotides in length with limited protein-coding potential. In addition to their possible role in cancer biology, circulating lncRNAs have emerged as a new class of promising cancer biomarkers, with independent studies demonstrating the feasibility of their use as tools in the diagnosis and prognosis of different types of malignancies and for predicting and possibly monitoring treatment response. However, critical issues are represented by nonuniform sample choice, handling and processing, blood cell contamination during sample preparation and the lack of consensus regarding data normalization. In this review, we discuss the value of circulating lncRNAs in the clinical setting, particularly with respect to their possible implementation as diagnostic and prognostic markers in cancer. Although the great potential of circulating lncRNAs as cancer biomarkers would be an important development in disease management, both intrinsic and extrinsic factors that may affect their measurement have not been fully characterized. Moreover, the clinical significance of circulating lncRNA may not be proven without a global consensus regarding procedures and standardized protocols for their detection.
Highlights
Contrary to the original expectation that higher mammals would have a greater number of genes, it is clear that the number of protein-coding genes is similar between humans and mice [1]
We focus on studies and technical issues concerning the evaluation of circulating long non-coding RNAs (lncRNAs) and their potential as biomarkers for cancer
The discovery of circulating lncRNAs has enabled a new understanding of the basic mechanisms of oncogenesis and opened up exciting prospects for diagnostics and prognostics
Summary
Contrary to the original expectation that higher mammals would have a greater number of genes, it is clear that the number of protein-coding genes is similar between humans and mice [1]. The complexity of a species is more closely associated with the number of non-coding RNAs (ncRNAs) than with the number of protein-coding genes [2], and the role of such ncRNAs in modulating gene expression has long been recognized. Various classes of ncRNAs with different targets and functions have been identified [3, 4], and these molecules can be grouped into two major classes: small non-coding RNAs, including microRNAs (miRNAs), which are perhaps the best described [5]; and long non-coding RNAs (lncRNAs), which were only recently discovered [6, 7]. LncRNAs are classically defined as RNA transcripts greater than 200 nucleotides in length that have no or limited protein-coding potential. The precise mechanism of lncRNA release into the extracellular environment is not completely understood, recent studies have suggested that some lncRNAs are
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