Classification of heterogeneous genetic variations of microRNA regulome in cancer.

Genetic variations and differential expression of miRNA regulome components are associated with cancer. Thus miRNA based diagnosis and treatments have been proposed. However, to better explore these options, the molecular changes in miRNA regulome must be understood. MicroRNAs can be involved in regulation of oncogenes and tumour suppressors. As each miRNA targets broad range of genes, minor changes in miRNAs can have great effects, contributing to cell transformation. Many genetic variants of miRNA regulome have been reported to be associated with cancer, but this information needs to be systematized. Therefore, we here classify different types of genetic variations of miRNA regulome in cancer. Genetic variations are comprised of structural and short polymorphisms and changes in epigenetic landscape. Additionally, unexplained differential expression is often reported. These alterations affect miRNA genes and their regulatory elements, processing machinery, degradation machinery, and targets, leading to changes in miRNA silencing. However, miRNA regulome components are not equally explored. A systematic overview over miRNA regulome can contribute to more targeted study design and understanding of miRNA function. We also present treatments and diagnosis based on miRNA regulome genetic variability and expression.