MicroRNA-based Cancer Therapeutics: Big Hope from Small RNAs

Abstract

Tremendous progress has been made during the last few years in identification of novel tumor-associated microRNAs and experimental validation of their cancer relevant gene targets. Indeed, these small non-coding RNAs are now known to modulate many biological pathways related to cancer progression, metastasis and therapy-resistance. Therefore, modulating miRNA functions may provide novel therapeutic opportunities for cancer treatment. This article reviews recent literature on the role of miRNAs in cancer with an emphasis on their potential as cancer therapeutics.

Figure 1. MicroRNA biogenesis and mechanisms of gene silencing

MicroRNA (miRNA) genes are generally transcribed by RNA polymerase II/III in nucleus to form large primary transcript (pri-miRNA). These pri-miRNA transcripts are processed to release the ~70-nucleotide hairpin RNA known as precursor-miRNA (pre-miRNA), which is transported to the cytoplasm and undergoes another processing to yield a transient ~22- nucleotide RNA duplex. RNA duplex is unwound into a mature single-stranded miRNA, and loaded into RNA-induced silencing complex (RISC). miRNA then binds to complementary sites in the 3’-untranslated region (3’-UTR) of target mRNA and regulate its expression either by causing degradation of mRNA or repression of their translation, depending on the degree of complementarity between the miRNA and its target.

Figure 2. miRNA-based therapeutic strategies against cancer

Inhibiting the function of oncomirs by use of anti-miR oligonucleotides (AMOs), small molecule inhibitors, miRNA sponges and miRNA masks/target protectors, and promoting the activity of anti-oncomirs through gene therapy or delivery of miRNA mimics can serve as novel therapeutic options against cancer.