Dataset Information


MiR-25 Tough Decoy Enhances Cardiac Function in Heart Failure.

ABSTRACT: MicroRNAs are promising therapeutic targets, because their inhibition has the potential to normalize gene expression in diseased states. Recently, our group found that miR-25 is a key SERCA2a regulating microRNA, and we showed that multiple injections of antagomirs against miR-25 enhance cardiac contractility and function through SERCA2a restoration in a murine heart failure model. However, for clinical application, a more stable suppressor of miR-25 would be desirable. Tough Decoy (TuD) inhibitors are emerging as a highly effective method for microRNA inhibition due to their resistance to endonucleolytic degradation, high miRNA binding affinity, and efficient delivery. We generated a miR-25 TuD inhibitor and subcloned it into a cardiotropic AAV9 vector to evaluate its efficacy. The AAV9 TuD showed selective inhibition of miR-25 in vitro cardiomyoblast culture. In vivo, AAV9-miR-25 TuD delivered to the murine pressure-overload heart failure model selectively decreased expression of miR-25, increased levels of SERCA2a protein, and ameliorated cardiac dysfunction and fibrosis. Our data indicate that miR-25 TuD is an effective long-term suppressor of miR-25 and a promising therapeutic candidate to treat heart failure.


PROVIDER: S-EPMC5910658 | BioStudies | 2018-01-01

REPOSITORIES: biostudies

Similar Datasets

2012-01-01 | S-EPMC3341631 | BioStudies
| S-EPMC6205728 | BioStudies
2014-01-01 | S-EPMC4131725 | BioStudies
1000-01-01 | S-EPMC3666623 | BioStudies
2009-01-01 | S-EPMC4298485 | BioStudies
1000-01-01 | S-EPMC3119354 | BioStudies
2012-01-01 | S-EPMC3420816 | BioStudies
2012-01-01 | S-EPMC3409693 | BioStudies
1000-01-01 | S-EPMC4208582 | BioStudies
2012-01-01 | S-EPMC3338799 | BioStudies