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Review
. 2014 Jul-Aug;5(4):537-48.
doi: 10.1002/wrna.1229. Epub 2014 Mar 28.

MicroRNAs as therapeutic targets in human cancers

Maitri Y Shah  1 , George A Calin
Affiliations
Review

MicroRNAs as therapeutic targets in human cancers

Maitri Y Shah et al. Wiley Interdiscip Rev RNA. 2014 Jul-Aug.

Abstract

MicroRNAs (miRNAs) are evolutionarily conserved, small, regulatory RNAs that negatively regulate gene expression. Extensive research in the last decade has implicated miRNAs as master regulators of cellular processes with essential role in cancer initiation, progression, and metastasis, making them promising therapeutic tools for cancer management. In this article, we will briefly review the structure, biogenesis, functions, and mechanism of action of these miRNAs, followed by a detailed analysis of the therapeutic potential of these miRNAs. We will focus on the strategies presently used for miRNA therapy; discuss their use and drawbacks; and the challenges and future directions for the development of miRNA-based therapy for human cancers.

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Figures

Figure 1
Figure 1
miRNA deregulation in human cancers. miRNA genes frequently undergo chromosomal deletions or translocations, epigenetic regulation, alterations in miRNA promoter activity by oncogenes and tumor suppressor genes or alterations in the miRNA processing machinery resulting in widespread deregulation in their expression. Consequently, oncogenic miRNAs are upregulated, while tumor suppressive miRNAs are downregulated. This alteration at the miRNAome leads to aberrant changes in the transcriptome and proteome, causing cellular transformation and tumor progression.
Figure 2
Figure 2
miRNA-based therapeutics for management of cancer. miRNA inhibition therapy for OncomiRs include antisense anti-miRs (AMOs, modified AMOs, LNA-based AMOs, antagomirs), small molecule inhibitors, miRNA sponges and miRNA masks. miRNA replacement therapy for tumor suppressive miRs includes miRNA mimics, small molecule enhancers and expression vectors. These approaches act at different stages of miRNA biogenesis, including processing, maturation and strand selection.
Figure 3
Figure 3
miRNA delivery options into the cells. Schematic representation of different delivery approaches currently investigated for delivery of miRNA-based therapeutics in cancer cells. Synthetic miRNAs can be delivered naked with different chemical modifications, conjugated to natural or synthetic polymers, conjugated with cholesterol molecules, complexed with liposomes, encapsulated in nanoparticles, using DNA-plasmid expression vectors or via viral expression vectors.
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