mir-17-92 Cluster is Required for and Sufficient to Induce Cardiomyocyte Proliferation in Postnatal and Adult Hearts

Rationale:Cardiomyocytes in adult mammalian hearts are terminally differentiated cells that have exited from the cell cycle and lost most of their proliferative capacity. Death of mature cardiomyocytes in pathological cardiac conditions and the lack of regeneration capacity of adult hearts are primary causes of heart failure and mortality. However, how cardiomyocyte proliferation in postnatal and adult hearts becomes suppressed remains largely unknown. The miR-17–92 cluster was initially identified as a human oncogene that promotes cell proliferation. However, its role in the heart remains unknown. Objective:To test the hypothesis that miR-17–92 participates in the regulation of cardiomyocyte proliferation in postnatal and adult hearts. Methods and Results:We deleted miR-17–92 cluster from embryonic and postnatal mouse hearts and demonstrated that miR-17–92 is required for cardiomyocyte proliferation in the heart. Transgenic overexpression of miR-17–92 in cardiomyocytes is sufficient to induce cardiomyocy...