The multiple molecular dimensions of long noncoding RNAs that regulate gene expression and tumorigenesis

LncRNAs are emerging as key regulators of gene expression and they ensure homeostasis during cell differentiation and development, replication, and adaptation to the environment. Because of their key central role in regulating the biology of living cells, it is crucial to characterize how lncRNAs function at the genetic, transcriptomic, and mechanistic level.

The low endogenous abundance and high molecular complexity of lncRNAs pose unique challenges for their characterization but new methodological advances in biochemistry, biophysics and cell biology have recently made it possible to characterize an increasing number of these transcripts, including oncogenic and tumor suppressor lncRNAs. These recent studies specifically address important issues that had remained controversial, such as the selectivity of lncRNA mechanisms of action, the functional importance of lncRNA sequences, secondary and tertiary structures, and the specificity of lncRNA interactions with proteins.

These recent achievements, coupled to population-wide medical and genomic approaches that connect lncRNAs with human diseases and to recent advances in RNA-targeted drug development, open unprecedented new perspectives for exploiting lncRNAs as pharmacological targets or biomarkers to monitor and cure cancer, in addition to metabolic, developmental and cardiovascular diseases.