Figure 1. Overview of oncomiRs or tumor suppressive miRNAs encoded as monocistronic or polycistronic genes, their involvement in tumorigenesis, and potential use as miRNA-based cancer therapeutics.

(A) A monocistronic miRNA gene encodes a transcript containing a single primary miRNA. In cancers, one mechanism to alter the abundance of a mature miRNAs is through changes in transcription of the primary miRNA, where the expression of a tumor suppressive miRNA is downregulated, while that of an oncomiR is enhanced. A tumor-suppressive miRNA typically targets transcripts encoding oncogenic proteins, therefore miRNA replacement therapies using tumor suppressive miRNA mimics are currently being tested. OncomiRs on the other hand target tumor suppressor protein transcripts, and hence their inhibition via antagomiRs is also a potential miRNA-based therapeutic strategy. (B) Transcription of a polycistronic miRNA gene or a miRNA cluster results in a primary miRNA transcript containing multiple miRNAs. The duplication of a cluster, and expression of a more or less intact cluster from multiple genomic loci generates paralogous miRNAs. The resultant miRNAs from paralogues can be predominantly tumor-suppressive or oncogenic; however, their function is often largely context dependent – i.e. tissue-specific, temporally regulated, etc. The potential therapeutic strategy targeting miRNAs expressed from clusters depends on the abundance of the individual tumor suppressive or oncogenic miRNAs. Combinatorial miRNA therapeutics is a potential strategy currently being evaluated to combat tumorigenesis where the altered ratio between oncogenic/tumor suppressive miRNAs drives cancer development.