Abstract 309: MiR-31a-5p Controls Cardiomyocyte Proliferation in Postnatal Hearts

Backgroud: MicroRNAs (miRNAs, miRs) are a class of endogenous non-codingRNAs, participating in a variety of essential biological processes including development, differentiation, proliferation and apoptosis. Rodents have the capacity to regenerate their hearts in response to injury while the capacity would be lost 7 day after birth, suggesting that mammals gradually lose their regenerative potential during postnatal development. The roles of miRNAs in regulating cardiomyocyte proliferation in postnatal hearts are largely unclear. Methods and Results: Cardiomyocytes were isolated from rat at day 0 and day 10. Agilent rat miRNA arrays were performed to determine the dysregulated miRNAs in cardiomyocytes between day 0 and day 10. A total of 32 miRNAs were found to be dysregulated between day 0 and day 10 (Fold change over 2 and P values less than 0.05). As determined by quantitative reverse transcription polymerase chain reactions and functional assays using EdU staining and Ki-67 staining, miR-31a-5p was found to be able to promote neonatal cardiomyocyte proliferation. Moreover, the expression of proliferation maker- Proliferating Cell Nuclear Antigen (PCNA) was also increased in cardiomyocytes transfected with miR-31a-5p mimics as determined by PCRs and Western blotting analysis. Tumor suppressor RhoBTB1 was found to be negatively regulated by miR-31a-5p in cardiomyocytes and also was responsible for the pro-proliferation effects of miR-31a-5p in neonatal cardiomyocytes. Conclusions: These studies demonstrate that miR-31a-5p regulates cardiomyocytes proliferation in postnatal hearts by targeting RhoBTB1. miR-31a-5p represents a therapeutic target for cardiac repair and regeneration.