Introduction: MicroRNAs (miRNAs) are small endogenous non-coding RNAs that repress the expression of their target genes by reducing mRNA stability and/or inhibiting translation. miRNAs are known to be aberrantly regulated in cancers. Modulators of miRNA (mimics and antagonists) have emerged as novel therapeutic tools for cancer treatment.Areas covered: This review summarizes the various strategies that have been applied to correct the dysregulated miRNA in cancer cells. The authors also discuss the recent advances in the technical development and preclinical/clinical evaluation of miRNA-based therapeutic agents.Expert opinion: Application of miRNA-based therapeutics for cancer treatment is appealing because they are able to modulate multiple dysregulated genes and/or signaling pathways in cancer cells. Major obstacles hindering their clinical development include drug delivery, off-target effects, efficacious dose determination, and safety. Tumor site-specific delivery of novel miRNA therapeutics may help to minimize off-target effects and toxicity. Combination of miRNA therapeutics with other anticancer treatment modalities could provide a synergistic effect, thus allowing the use of lower dose, minimizing off-target effects, and improving the overall safety profile in cancer patients. It is critical to identify individual miRNAs with cancer type-specific and context-specific regulation of oncogenes and tumor-suppressor genes in order to facilitate the precise use of miRNA anticancer therapeutics.
Keywords: Antisense oligonucleotide; CRISPR/Cas9 gene editing; N-acetylgalactosamine; artificial ribonucleases; extracellular vesicles; microRNA masking oligonucleotides; microRNA mimic; microRNA sponges; small RNA zippers.