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The ability of individual miRNAs to regulate multiple target genes, implicated in turn in several pathways, confers them an extraordinary capacity as multifunctional tools for cancer therapy. Thus, restoration of the level of a single or few pleiotropic miRNAs could eventually re-establish molecular pathways altered in cancer, providing a more effective therapeutic strategy. However, further studies will be needed to validate the preliminary successful results of miRNA-based therapy obtained in cellular and animal models. Also, it is crucial to expand our knowledge about the molecular regulation of the miRNome (global miRNA expression levels) in physiological and pathological settings.