Previously thought of as junk transcripts and pseudogene remnants, long non-coding RNAs (lncRNAs) have come into their own over the last decade as an essential component of cellular activity, regulating a plethora of functions within multicellular organisms. lncRNAs are now known to participate in development, cellular homeostasis, immunological processes, and the development of disease. With the advent of next generation sequencing technology, hundreds of thousands of lncRNAs have been identified. However, movement beyond mere discovery to the understanding of molecular processes has been stymied by the complicated genomic structure, tissue-restricted expression, and diverse regulatory roles lncRNAs play. In this review, we will focus on lncRNAs involved in lung cancer, the most common cause of cancer-related death in the United States and worldwide. We will summarize their various methods of discovery, provide consensus rankings of deregulated lncRNAs in lung cancer, and describe in detail the limited functional analysis that has been undertaken so far.
RECOGNITION FOR THE DIVERSITY OF LNCRNAS AND THEIR INVOLVEMENT IN CANCERThe first lncRNA was discovered decades ago during the characterization of X-chromosome inactivation [1]. Following that early discovery, several lncRNAs were inadvertently uncovered and characterized as anomalous molecules before the community recognized that lncRNAs represent a distinct class of regulatory RNAs. With the completion of the human genome project in 2003 and subsequent characterization the genomic landscape, attempts at bioinformatics prediction of mRNA genes was found to be cluttered with many fold higher predicted transcripts than were experimentally verified as the precursors of proteins [2][3][4][5]. What these programs revealed was a glut of predicted transcripts, genes with hallmarks of transcription but no discernable protein coding function. In addition, these were thought to have no practical biological function because they had little evolutionary conservation [6]. Initially, these unverified genes were dismissed as programming artifacts to be eliminated [7][8][9]. However, it was quickly realized the lack of evolutionary conservation did not rule out function [10]. It is now accepted that the human genome contains many thousands of lncRNA transcripts. Functional implications of this discovery have yet to be fully elucidated. To date lncRNAs have been detected throughout development and in every cell type tested thus far.One field that has been particularly active in lncRNA discovery is cancer biology. Due to the pressing need for development of novel therapeutics and diagnostics, many newly emergent fields have been focused on cancer research. These include the discovery of microRNAs, targeted immunotherapy, and most recently circulating tumor cells. Added to this ever-growing list are lncRNAs. Their implication in a diverse array of regulatory roles has heightened interest in these molecules as functional players in the development and heterogeneity of can...