MicroRNAs in Cancer Therapy: From Bench to Bedside

Srikumar      Sengupta; Anupam      Bishayee

Abstract

MicroRNAs (miRNAs) are short (∼22 nucleotides), highly conserved non-coding RNA molecules that bind to sequences in the 3 untranslated region (3 UTR) of genes with full or partial complementarity, leading to their degradation and/or translational inhibition. Dysregulation of miRNA expression is associated with several human cancers and accumulation of these molecules differs significantly between normal and neoplastic cells. Several miRNAs act as oncogenes by inhibiting tumor suppressors and are over-expressed in cancers, whereas others function as tumor suppressors by inhibiting oncogenes, and are down-regulated or lost in cancers. Moreover, many miRNAs regulate multiple genes associated with one or more cancer pathways, acting as “master switches”, making them ideal targets for the treatment of this disease. Modified RNA molecules that resist nuclease degradation and mimic miRNAs or inactivate them through binding with strong affinity inhibit cancer growth and progression in animal models. The success of repressing neoplastic growth by targeting miRNAs in vivo provides an exciting prospect of using these molecules in cancer therapeutics. Here we review the current data on the involvement of miRNAs in cancer, their mechanism of action and role as “master switches”. In this review, we also discuss the prospect of targeting these “master switches” in therapeutic intervention of this disease, highlighting miRNA-based successful cancer therapy in preclinical animal models and its challenges. We finally conclude by discussing the potential of using dietary agents to modulate expression of miRNAs in cancer.

Keywords: microRNA, miRNA, cancer treatment, oncomir, antimiR, antagomir, miRNA therapy

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