MicroRNAs and cancer therapy: the next wave or here to stay?

Abstract

MicroRNAs are small, non-coding RNAs that regulate gene expression by degrading and/or suppressing the translation of target mRNA by Watson-Crick base pairing in the 3-'UTR of mRNA. The recent explosion of information about the biochemistry and action of microRNAs has implicated these regulatory molecules in many unexpected biologic processes, ranging from development and homeostasis to diseases such as cancer. In general, microRNAs are down regulated or deleted in cancer while a few are upregulated. However, some microRNAs suppress oncogenesis or metastasis, while others are involved in promoting tumorigenesis. All these developments make microRNAs attractive diagnostic markers as well as therapeutic targets. Here we will briefly review the opportunities and potential limitations of using microRNAs in cancer therapeutics.

Figure 1

MicroRNA biogenesis. Functional microRNA’s are generated from the large mRNA’s, with 5′ Cap and 3′Poly Adenylation, mainly transcribed by RNA Pol II. Large mRNAs fold by complementary base pairing to form several stem loop structures, known as Pri-mRNA. The RNA endonuclease Drosha recognizes the appropriate stem loop structures and cleaves them to form Pre-mRNA of ~70nucleotides in length, which are exported to cytoplasm by Exportin5. The RNase III Endonuclease, Dicer cleaves the loop structure of Pre-miRNA to form small RNA duplexes of ~22 nucleotides. The short lived RNA duplex is incorporated into RNA-induced silencing complex (RISC), where a single functional miRNA strand is selected to elicit RNA interference by complementary base pairing with the target mRNAs in 3′UTRs. If the base pairing is perfect the target mRNAs are subjected to degradation by nucleases and otherwise lead to translational repression.