ABSTRACT
Analyses of human genome revealed that almost 98% of the genetic material does not code for proteins. Part of this non-coding genome is transcribed into a fascinating repertoire of functional non-protein-coding RNAs (ncRNAs) (Eddy 2001; Mattick 2009). In fact, most human transcriptional units are ncRNAs (Bertone et al. 2004; Birney et al. 2007; Consortium et al. 2007). Until three decades ago, transfer RNA (tRNA) and ribosomal RNA (rRNA), were the most prominent members of ncRNAs, both involved in the biosynthesis of proteins. Th e discovery that RNAs are able to catalyze biochemical reactions, such as cleavage and ligation of RNA molecules, or the formation of the peptide bond, expanded the repertoire of ncRNAs (Rossi 1992; Nissen et al. 2000). Apart their “processive” role, the discovery of the RNA interference mechanism (RNAi) revealed that specifi c ncRNAs are major posttranscriptional regulators of gene expression. Th e latter constitute a class of short (~19-28 nt in length) RNAs produced by double stranded RNA processing. Th e short length of such regulatory ncRNAs compared to other RNA types christened these as microRNAs (miRNAs), short interfering RNAs (siRNAs), small nucleolar RNAs (snoRNAs), small modulatory RNAs (smRNAs) and tiny non-coding RNAs (tncRNAs) (Lagos-Quintana et al. 2001; Lau et al. 2001; Lee and Ambros 2001; Kim 2005b). Apart the short ncRNAs, genome-wide surveys have recently revealed that eukaryotic genomes are extensively transcribed into thousands of transcripts much longer (>200 nt) than the “traditional” short, conserved ncRNAs, adding a new subclass, namely long non-coding RNAs (lncRNAs). lncRNAs are thus far implicated in gene-regulatory roles, such as transcription, splicing, translation and others (Guttman et al. 2009; Mattick 2009; Ponting et al. 2009; Wilusz et al. 2009). Of the vast repertoire of ncRNAs, miRNAs have been extensively studied due to their involvement in biological pathways and diseases. More than one thousand miRNAs have been identifi ed so far, and have been shown to regulate more than 60% of human protein-coding genes (Friedman et al. 2009; Sayed and Abdellatif 2011). Th e link of miRNAs to cancer is attributed to sequences transcribed to miRNAs that locate in genomic regions involved in cancer, as well as to their deregulated expression profi les in malignancies (Calin et al. 2004a; Calin et al. 2004b; Lu et al. 2005). Hence, miRNAs have emerged as important prognostic and diagnostic markers, as well as to therapeutic targets against cancer with increasing potential. Herein, we focus on the biogenesis, the mechanisms of miRNA-mediated gene silencing and the recent advances of miRNAs as cancer biomarkers.
