Development of MicroRNAs as Potential Therapeutics against Cancer

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that function at the posttranscriptional level in the cellular regulation process. miRNA expression exerts vital effects on cell growth such as cell proliferation and survival. In cancers, miRNAs have been shown to initiate carcinogenesis, where overexpression of oncogenic miRNAs (oncomiRs) or reduced expression of tumor suppressor miRNAs has been reported. In this review, we discuss the involvement of miRNAs in tumorigenesis, the role of synthetic miRNAs as either mimics or antagomirs to overcome cancer growth, miRNA delivery, and approaches to enhance their therapeutic potentials.

Figure 1

MicroRNA biogenesis pathway. miRNA genes are transcribed to produce primary miRNA transcript (pri-miRNA) by RNA polymerase II and cleaved into precursor miRNA transcript (pre-miRNA) by the microprocessor complex Drosha-DGCR8 in the nucleus. The pre-miRNA is then exported into the cytoplasm by Exportin-5 where it is processed into miRNA duplex by Dicer and its interacting partner, TRBP. The miRNA duplex is then unwound into two single-stranded miRNAs. The functional strand of mature miRNA is uploaded onto the RNA-induced silencing complex (RISC) and negatively regulates gene expression resulting in either target mRNA degradation or translation repression, while the passenger strand is degraded.