Novel approaches toward managing the micromanagers: ‘non-toxic’ but effective

Many common diseases that plague our civilized society, such as heart disease, cancer, metabolic and inammatory disease are of complex nature and involve the dysregulation of multiple genes at any given time. In a world of increasingly complex disease etiologies, microRNAs are rapidly gaining recognition as either the root cause of certain diseases, as a novel diagnostic tool or as an essential therapeutic target. MiRNAs are small, non-coding RNAs that are highly conserved among species and contribute to more than 4% of all human genes.1,2 Most miRNAs have only weak effects on gene expression, allowing for precise expression control and reduction of expression noise.35 The ability of miRNAs to ne-tune mRNA expression proles during cellular differentiation, evolution and development, and at the crucial balance between cancer cell apoptosis and proliferation has prompted a comparison with a rheostat and resulted in the nickname micromanagers of gene expression.6,7 Current knowledge indicates that the expression of thousands of mRNAs in each cell type is controlled by armies of miRNA micromanagers, and that during the diseases mentioned above these micromanagers are somewhat out of control.