The Primary Role of Noncoding RNA in the Pathogenesis of Cancer

The discovery of oncogenes and tumor suppressor genes provided important insights into the molecular pathogenesis of cancer but also revealed some contradictions in the prevailing somatic mutation theory. The evidence that noncoding RNAs (ncRNAs) form an elaborate network that regulates the flow of genetic information in eukaryotic cells offers an explanation for the inconsistencies. ncRNAs comprise a wide variety of molecules that interact with one another as well as with other RNAs, DNA, and proteins, over whose activities they exert a regulatory influence. The outcome of the dynamic interactions of the cell's biomolecules is the emergence of higher-order states of equilibrium, called attractor states, which correspond to the gene-expression configurations of distinct cell types. Attractor states are relatively stable systems, but they are susceptible to perturbation by a disturbing force, such as mutation. Mutations that disrupt the ncRNA network can enable the cell to undergo a state transition towards a potentially neoplastic one. This is the crux of tumorigenesis. An inquiry into the architecture of the ncRNA network and its role in tumorigenesis is required to complement our knowledge of the well-known cancer genes as well as serve as a guide in the design of new anticancer therapeutics.