Function of many genes is governed by the flow of genetic information from DNA to RNA to protein, the central dogma of molecular biology. On the other hand, non-coding regions of the genome are pervasively transcribed and yield thousands of non-coding RNAs (ncRNAs). MicroRNAs (miRNAs) are abundant class of small ncRNAs with 21-25 nucleotides length. The first miRNA was discovered in 1993, and miRNA research was further accelerated by the Fire and Mello’s discovery of RNA interference (RNAi) in 1998.
In mammalian cells, the biogenesis of miRNAs is mediated by multiple biochemical steps including processing of miRNA precursors by two RNase III enzymes, Drosha and Dicer, and formation of RNA-induced silencing complex with Argonaute (Ago) proteins. miRNAs embedded in Ago proteins recognize their binding sequences predominantly located in 3’UTRs of target mRNAs through sequence complementarity between 5’ seed regions of miRNAs (nt 2-7) and their binding sites and suppress their expression. Reflecting the short sequence dependency, individual miRNAs regulate hundreds of target genes, thus forming complex gene regulatory networks. In addition to regulation of normal cells, miRNAs are known to modulate various pathological processes including cancer. We have investigated the relationships between cancer, miRNA biogenesis, and miRNA-mediated gene regulation and revealed the roles of tumor suppressor p53 in miRNA processing (Suzuki et al, Nature, 2009; Suzuki et al, Mol Cell, 2011).
In cancer biology, numerous studies have reported that miRNAs regulate many aspects of autonomous behavior of cancer cells, including sustained proliferation, resistance to cell death, and acquisition of metastasis phenotypes. We also previously reported that miRNAs regulate immune phenotypes of malignant lymphoma cells and modulate surrounding tumor microenvironments, illuminating miRNA-mediated non-cell-autonomous mechanism in cancer progression (Matsuyama et al, Blood, 2011; Suzuki et al, Oncogene, 2015).