The MicroRNA Decalogue of Cancer Involvement

MicroRNAs (miRNAs) are short (19-24 nucleotides in length) non-coding RNAs (ncRNAs) that posttranscriptionally regulate gene expression. In this chapter, the fundamentals for understanding miRNA involvement in human cancers are summarized as the decalogue of miRNA principles: (1) miRNAs can up- or down-regulate gene expression by targeting various genic regions; (2) each miRNA can regulate the expression of numerous target genes, and conversely, multiple miRNAs can regulate the same target gene, and this interplay is involved in the regulation of various physiological processes and pathophysiology of many diseases, including all analyzed types of human cancers; (3) about half of mammalian miRNAs are intragenic, predominantly intronic, and can be coordinately expressed and functionally linked with their host genes; (4) miRNAs are frequently located within cancer-associated genomic regions (CAGRs) and act as tumor suppressors or oncogenes; (5) genetic variations within miRNA genes, their targets, and genes encoding components of processing machinery can affect phenotypic variation and disease susceptibility; (6) miRNA-mediated gene silencing is one of the classes of epigenetic mechanisms and, together with DNA methylation and histone modifications, functions in an interacting regulatory circuit; (7) aberrant miRNA gene expression signatures characterize cancer cells and are as such valuable biomarkers applied in the diagnosis, prognosis, and treatment of cancer; (8) circulating miRNAs have been shown as non-invasive biomarkers in cancer; (9) RNA inhibition using miRNAs is a potential treatment method that can be applied for specific types of cancer; and (10) interplay between miRNAs, other ncRNAs, and protein-coding genes forms a complex network of interactions in normal and disease tissues. Understanding the overall functional roles of miRNAs in cancer is therefore important not only for scientists but also for clinicians and oncologists. It may also have a major impact on biomedical research by providing miRNA-based therapeutic and diagnostic opportunities.