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Publication : Cmarr/miR-540-3p axis promotes cardiomyocyte maturation transition by orchestrating Dtna expression.

First Author  Wu Y Year  2022
Journal  Mol Ther Nucleic Acids Volume  29
Pages  481-497 PubMed ID  36035750
Mgi Jnum  J:356160 Mgi Id  MGI:7762252
Doi  10.1016/j.omtn.2022.07.022 Citation  Wu Y, et al. (2022) Cmarr/miR-540-3p axis promotes cardiomyocyte maturation transition by orchestrating Dtna expression. Mol Ther Nucleic Acids 29:481-497
abstractText  The immature phenotype of embryonic stem cell-derived cardiomyocytes (ESC-CMs) limits their application. However, the molecular mechanisms of cardiomyocyte maturation remain largely unexplored. This study found that overexpression of long noncoding RNA (lncRNA)-Cmarr, which was highly expressed in cardiomyocytes, promoted the maturation change and physiological maturation of mouse ESC-CMs (mESC-CMs). Moreover, transplantation of cardiac patch overexpressing Cmarr exhibited better retention of mESC-CMs, reduced infarct area by enhancing vascular density in the host heart, and improved cardiac function in mice after myocardial infarction. Mechanism studies identified that Cmarr acted as a competitive endogenous RNA to impede the repression of miR-540-3p on Dtna expression and promoted the binding of the dystrophin-glycoprotein complex (DGC) and yes-associated protein (YAP), which in turn reduced the proportion of nuclear YAP and the expression of YAP target genes. Therefore, this study revealed the function and mechanism of Cmarr in promoting cardiomyocyte maturation and provided a lncRNA that can be used as a functional factor in the construction of cardiac patches for the treatment of myocardial infarction.
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