Long non-coding RNAs: new opportunities and old challenges in cancer therapy

The investigation of long non-protein-coding RNAs (lncRNAs) has become a key area in biological and biomedical research. This is the result of sequencing and analysis of the human genome, which showed that only around 2% encodes proteins, together with the analysis of RNA transcripts (the transcriptome), which showed that a further 80% or so of the genome is actively transcribed (1,2). Consequently, it is now clear that most of the human genome largely encodes non-protein-coding RNAs, most of which, at greater than 200 nucleotides, are classified as lncRNAs. Although we are only just beginning to analyse this vast number of transcripts, it is already evident that many lncRNAs play crucial roles in human molecular cell biology ranging from providing essential frameworks for RNA processing, through the epigenetic control of gene expression, to blocking and regulating cell signalling pathways [reviewed by Morris and Mattick (3)]. It is not surprising therefore that dysfunction in many lncRNAs has already been strongly implicated in oncogenesis and in the development of resistance to cancer therapy (4). Such a profound advance in our understanding of human cell physiology and pathology will clearly present many opportunities for the development of entirely novel cancer therapies.