ABSTRACT
MicroRNAs (miRNA) comprise of a class of short noncoding RNAs that are 18-25 nucleotides in length found in all animal and plant cells. In 1993, the fi rst miRNAs were recognized in Caenorhabditis elegans by Lau et al (Lau et al. 2001). Later on, various small regulatory RNAs were discovered in plants and mammals and designated as ‘microRNA’ (Lagos-Quintana et al. 2003, Lagos-Quintana et al. 2001). Currently, more than 1200 human miRNAs are registered in the miRBase database and have been extensively studied for their involvement in RNA interference (RNAi) i.e. how they regulate gene expression post-transcriptionally, and how they contribute to diverse physiological and pathological functions (Bartel 2004). The biogenesis and RNAi functions of miRNA (i.e. how miRNAs are generated and processed
into a mature form, and how they regulate gene expression) have been intensively investigated and well-described. Furthermore, developments in miRNA-related technologies, such as miRNA expression profi ling and synthetic oligoRNA, have contributed to the identifi cation of miRNAs involved in a number of physiological and pathological phenotypes. A Pubmed search for microRNAs returns 15,549 hits (on July 2, 2012), similarly key words microRNA and cancer return 5,711 research articles. Most striking is the observation that research publications from 2000 to 2011 show an exponential increase in research indicating that the fi eld is advancing rapidly. These studies have led to a deeper understanding of microRNA biogenesis, their regulatory control on different genes and strategies to target them for anti-cancer therapeutic benefi ts. There has been a drive at the pharmaceutical front to identify and target miRNAs for therapeutic benefi t. A number of strategies have been proposed as potential miRNA targeted therapy and these include, anti-sense to miRNA target sequence, pre miRNA synthetic oligonucleotide, peptide nucleic acids (PNAs) and many more (Garzon et al. 2010). Nevertheless, the design of pre-and anti-miRNA agents is not as straightforward as originally thought because key questions remain largely unanswered, such as how miRNA expression is controlled and which genes are regulated by each miRNA. Additionally it is not known whether individual miRNAs regulate certain set of genes in isolation or they are part of a complex network and work in tandem with other miRNA. Additional degree of complexity is added by the recent fi nding that a majority of miRNAs are regulated epigenetically as well (Sato et al. 2011). Here, we will introduce the concept that novel integrated technologies such as systems biology and network modeling can be utilized for better understanding of the complex interaction network between miRNAs and that will, in turn, aid in the design of personalized miRNA based therapy.
