MicroRNA and Cancer

The broad goal of the 2007 Forbeck Symposium was to examine the relationship between microRNAs and cancer. The past few years have seen a veritable revolution in biology, with the discovery that small RNAs act in a broad range of biological processes and pathways. In the expanding world of small RNAs, microRNAs hold a special place in that they are evolutionarily conserved regulators of gene expression networks. These ~18-22 nucleotide, single stranded RNAs are derived from fairly conventional genes, with the exception being that the end-product of the gene is a small, non-coding RNA rather than an encoded protein. Standard transcriptional regulatory circuits govern the synthesis of the primary microRNA transcript, which is then processed through two steps to yield a mature small RNA. These small RNAs join RISC, the core effector complex of the RNA interference (RNAi) pathway, associating specifically with an Argonaute protein. The Argonaute protein uses the small RNA as a guide to select silencing targets based upon sequence complementarity between the small RNA and a target messenger RNA. Through such interactions, each microRNA can regulate the expression of potentially hundreds of genes. While the human genome harbors 20- 30,000 protein-coding genes, microRNAs are numbered in the hundreds. However, this number, combined with broad target profiles, gives microRNAs potentially quite large roles in regulating the biology of an organism.