MiRNA-based therapeutic intervention of cancer

Abstract

MicroRNAs (miRNAs) are important modulators of eukaryotic gene expression. By targeting protein coding transcripts, miRNAs influence the cellular transcriptome and proteome, thus helping to determine cell fate. MiRNAs have emerged as crucial molecules in cancer research, in which recent studies have linked erratic expression of miRNAs to carcinogenesis and have provided solid evidence for their potential in cancer therapy. This review briefly summarises the recent knowledge on the involvement of miRNAs in tumourigenesis and reviews current studies on the therapeutic strategies and advances in the delivery of miRNAs.

Fig. 1

The majority of miRNA genes are transcribed by the RNA polymerase II (Pol II) as primary miRNAs (pri-miRNAs) which are processed to precursor miRNAs (pre-miRNAs) via the Drosha-DGR8 complex. Pre-mRNAs are exported to the cytoplasm by Exportin-5-Ran-GTP (Xpo-5-RanGTP) where Dicer1 cleaves the hairpin loop and Tar RNA-binding protein 2 (TARBP2) facilitates the RNA duplex loading onto Argonaute protein AGO2. AGO2 and the mature strand enter a protein effector complex formed by the RNA-induced silencing complex (miRISC). The miRNA guides the RISC to messenger RNA targets causing either mRNA cleavage (perfect complementarity) or translational repression (imperfect complementarity)