Abstract 107: MicroRNA-31: A Novel Therapeutic Target for Ischemic Heart Disease

MicroRNAs (miRNA), small sequences of non-coding RNA which interact with complementary sequences on the 3’untranslated region of target messenger RNAs to modulate translation, have a pivotal role in the development of the heart and its response to injury. Myocardial infarction (MI) triggers a dynamic miRNA response with the potential of yielding therapeutic targets. Following miRNA array profiling in rat hearts 2, 7 and 14 days after MI induced by coronary ligation, we identified a progressive time-dependent up-regulation of miR-31 compared to sham rats. Increase of miR-31 in heart tissue in the acute and subacute phases after MI (up to 90-fold) was also detected by Real-Time PCR (P=0.02 at day 2; P<0.0001 at days 7 and 14, vs. sham). We found that miR-31 has a repressive effect on tissue mRNA expression of cardiac troponin-T (TNNT2), E2F transcription factor 6 (E2F6) and mineralocorticoid receptor (NR3C2). Reporter gene assays showed that miR-31 targets the 3′UTR of these genes, with a marked repressive ...