| First Author | Bo L | Year | 2014 |
| Journal | Cell Death Differ | Volume | 21 |
| Issue | 6 | Pages | 967-77 |
| PubMed ID | 24531537 | Mgi Jnum | J:229335 |
| Mgi Id | MGI:5751640 | Doi | 10.1038/cdd.2014.18 |
| Citation | Bo L, et al. (2014) Autophagic program is regulated by miR-325. Cell Death Differ 21(6):967-77 |
| abstractText | Autophagy is required for the maintenance of cardiomyocytes homeostasis. However, the abnormal autophagy could lead to the development of heart failure. Autophagy is enhanced during myocardial ischemia/reperfusion; it remains to elucidate the molecular regulation of autophagy. We report here that miR-325, ARC and E2F1 constitute an axis that regulates autophagy. Our results showed that miR-325 expression is upregulated upon anoxia/reoxygenation and ischemia/reperfusion. Cardiomyocyte-specific overexpression of the miR-325 potentiates autophagic responses and myocardial infarct sizes, whereas knockdown of miR-325 inhibited autophagy and cell death. We searched for the downstream mediator of miR-325 and identified that ARC is a target of miR-325. ARC transgenic mice could attenuate autophagy and myocardial infarction sizes upon pressure-overload-induced heart failure, whereas ARC null mice exhibited an increased autophagic accumulation in the heart. The suppression of ARC by miR-325 led to its inability to repress autophagic program. In exploring the molecular mechanism by which miR-325 expression is regulated, our results revealed that the transcription factor E2F1 contributed to promote miR-325 expression. E2F1 null mice demonstrated reduced autophagy and myocardial infarction sizes upon ischemia/reperfusion. Our present study reveals a novel autophagic regulating model that is composed of E2F1, miR-325 and ARC. Modulation of their levels may provide a new approach for tackling cardiac failure. |
