Abstract
Noncoding RNAs (ncRNAs) constitute the majority of the human transcribed genome. This largest class of RNA transcripts plays diverse roles in a multitude of cellular processes, and has been implicated in many pathological conditions, especially cancer. The different subclasses of ncRNAs include microRNAs, a class of short ncRNAs; and a variety of long ncRNAs (lncRNAs), such as lincRNAs, antisense RNAs, pseudogenes, and circular RNAs. Many studies have demonstrated the involvement of these ncRNAs in competitive regulatory interactions, known as competing endogenous RNA (ceRNA) networks, whereby lncRNAs can act as microRNA decoys to modulate gene expression. These interactions are often interconnected, thus aberrant expression of any network component could derail the complex regulatory circuitry, culminating in cancer development and progression. Recent integrative analyses have provided evidence that new computational platforms and experimental approaches can be harnessed together to distinguish key ceRNA interactions in specific cancers, which could facilitate the identification of robust biomarkers and therapeutic targets, and hence, more effective cancer therapies and better patient outcome and survival.
Highlights
Recent advances in high-throughput sequencing technologies and computational platforms have been pivotal towards the discovery and classification of a class of RNA species, collectively known as the noncoding RNAs
Noncoding RNAs comprise a diverse range of RNA species, including rRNAs and others that can be further categorized into short ncRNAs and long ncRNAs (Figure 1)
The first miRNA, lin-4, was identified in Caenorhabditis elegans and has since sparked an avalanche of miRNA research leading to the characterization of its biogenesis, regulatory functions, and involvement in human diseases [9,10]. miRNAs are small ncRNAs around 22 nucleotides long and execute their post-transcriptional regulatory effects by binding to specific sites known as miRNA response elements (MREs) on their target transcripts, resulting in either transcript degradation or translational inhibition [11,12]
Summary
Recent advances in high-throughput sequencing technologies and computational platforms have been pivotal towards the discovery and classification of a class of RNA species, collectively known as the noncoding RNAs (ncRNAs). Other than mRNAs and transcribed pseudogenes, recent studies have shown that lncRNAs and circRNAs carry MREs and participate in ceRNA regulation [19,22] These observations add another dimension to the already complicated posttranscriptional landscape and highlight the importance of coding-independent functions of a large proportion of the transcriptome. Due to the non-canonical nature of the MREs, Gilot et al showed that miR-16 binding to TYRP1 does not induce decay, and instead, increases TYRP1 transcript expression, making TYRP1 a robust miR-16 decoy with oncogenic capacity in melanoma [42] These studies demonstrated that, when all criteria are met, it is physiologically possible to sponge even highly abundant miRNAs
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