Abstract
Mammalian cardiomyocytes undergo a critical hyperplastic-to-hypertrophic growth transition at early postnatal age, which is important in establishing normal physiological function of postnatal hearts. In the current study, we intended to explore the role of long non-coding (lnc) RNAs in this transitional stage. We analyzed lncRNA expression profiles in mouse hearts at postnatal day (P) 1, P7 and P28 via microarray. We identified 1,146 differentially expressed lncRNAs with more than 2.0-fold change when compared the expression profiles of P1 to P7, P1 to P28, and P7 to P28. The neighboring genes of these differentially expressed lncRNAs were mainly involved in DNA replication-associated biological processes. We were particularly interested in one novel cardiac-enriched lncRNA, ENSMUST00000117266, whose expression was dramatically down-regulated from P1 to P28 and was also sensitive to hypoxia, paraquat, and myocardial infarction. Knockdown ENSMUST00000117266 led to a significant increase of neonatal mouse cardiomyocytes in G0/G1 phase and reduction in G2/M phase, suggesting that ENSMUST00000117266 is involved in regulating cardiomyocyte proliferative activity and is likely associated with hyperplastic-to-hypertrophic growth transition. In conclusion, our data have identified a large group of lncRNAs presented in the early postnatal mouse heart. Some of these lncRNAs may have important functions in cardiac hyperplastic-to-hypertrophic growth transition.
Highlights
Pathogenesis of heart failure and cardiomyopathies[12,13,14,15,16,17,18]
We focused on one novel cardiac-enriched lncRNA, ENSMUST00000117266, which was likely involved in the hyperplastic-to-hypertrophic growth transition via its role in regulating cardiomyocyte proliferation
NAs in early postnatal hearts, lncRNA microarray was performed by using C57BL/6 J mouse hearts harvested at P1, P7 and P28
Summary
Pathogenesis of heart failure and cardiomyopathies[12,13,14,15,16,17,18]. Whether these lncRNAs are associated with hyperplastic-to-hypertrophic growth transition is largely unknown. We identified over thousands of lncRNAs via bioinfomatic analysis that were differentially expressed from P1 to P28. We validated 10 lncRNAs by qRT-PCR for their expression levels and tissue specificities. We focused on one novel cardiac-enriched lncRNA, ENSMUST00000117266, which was likely involved in the hyperplastic-to-hypertrophic growth transition via its role in regulating cardiomyocyte proliferation
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