Mir-92 Micro RNA Precursor Family - Gene Targets

Gene Targets

As miR recognition elements are typically found in the 3' UTR of the target gene mRNA, bioinformatics alone can identify putative miR-92 targets using resources such as miRGen database. In one report, miRanda software found 300 different genes that have putative miR-92a binding sites conserved among Homo sapiens, Mus musculus, and Rattus norvegicus at the 3' UTR regions of their transcripts. Two genes brought into the limelight by such means were ERβ and MUC16. Down regulation of oestrogen receptors β1 and α have been associated with various forms of breast cancer. While the mode of action of ERα is not well established there is strong evidence supporting a role for miR-92 within the regulatory pathway of ERβ1. Profiling different breast cancer cell lines against non cancerous control cell lines demonstrated a significant inverse relationship between expression of ERβ1 and miR-92. Specifically, MCF-7 breast cancer cell lines transfected with anti-miR-92 showed an increase in ERβ1 whereas transfection with pre-miR-92 (an antibody against the precursor of miR-92) resulted in down regulation of ERβ1. Similarly, and as a side experiment, the knock down of miR-92 had equivalent action of restoring MUC16 expression in the same cell type. Further evidence came when transfecting MCF-7 cells with a GFP reporter cloned to contain the ERβ1 3' UTR region. Flow cytometry revealed significant increase in green fluorescence upon transfection with anti-miR-92. This evidence suggests that miR-92 targets both ERβ1 and MUC16 mRNA and in doing so suppresses their expression.