Lung cancer biology has traditionally focused on genomic and epigenomic deregulation of protein-coding genes to identify oncogenes and tumor suppressors diagnostic and therapeutic targets. Another important layer of cancer biology has emerged in the form of noncoding RNAs (ncRNAs), which are major regulators of key cellular processes such as proliferation, RNA splicing, gene regulation, and apoptosis. In the past decade, microRNAs (miRNAs) have moved to the forefront of ncRNA cancer research, while the role of long noncoding RNAs (lncRNAs) is emerging. Here we review the mechanisms by which miRNAs and lncRNAs are deregulated in lung cancer, the technologies that can be applied to detect such alterations, and the clinical potential of these RNA species. An improved comprehension of lung cancer biology will come through the understanding of the interplay between deregulation of non-coding RNAs, the protein-coding genes they regulate, and how these interactions influence cellular networks and signalling pathways. 1. Introduction The human genome is comprised of less than 2% protein coding genes; however, more than 90% of the genome is transcribed, suggesting that the majority of the transcriptome is comprised of noncoding RNAs—transcripts that lack an open reading frame and as such do not encode a protein [1–4]. However this by no mean implies that ncRNAs lack function, but rather highlights the importance of looking beyond protein-coding genes in order to improve our knowledge of normal and disease biology. ncRNAs are loosely classified into two main categories: small non-coding RNAs (18–200 nucleotides), which includes transcripts such as miRNAs, transfer RNAs (tRNAs), small interfering RNAs (siRNAs), piwi-interacting RNAs (piRNAs) and some ribosomal RNAs, and long non-coding RNAs (lncRNAs) (200+ nucleotides), a family comprised of pseudogenes, antisense RNA and transcribed ultraconserved regions to name a few (Table 1) [4]. ncRNAs comprise a class of transcripts that until the last few decades was largely overlooked. While some are known to play important roles in the regulation of gene expression, splicing, epigenetic control, chromatin structure and nuclear transport, the function of most ncRNAs remains unknown [5, 6]. Of the species of ncRNAs identified to date, miRNAs, siRNAs, and piRNAs are the most thoroughly investigated. With roles in a number of cellular functions, it is not surprising that the deregulation of ncRNAs has been linked to human disease, including a number of cancers, such as breast, prostate, lung, colon, and liver. Increasing
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