| Cmarr/miR-540-3p axis promotes cardiomyocyte maturation transition by orchestrating Dtna expression |
| Author |
Wu, YK; Guo, XD; Han, T; Feng, K; Zhang, P; Xu, YX; Yang, YW; Xia, YC; Chen, Y; Xi, JJ; Yang, HT; Wan, XP; Kang, JH |
| Journal |
MOLECULAR THERAPY-NUCLEIC ACIDS |
| Pub Year |
2022 |
| Type |
Article |
| Abstract |
The immature phenotype of embryonic stem cell-derived cardi-omyocytes (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 ex-pressed 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 infarc-tion. 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. There-fore, 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 construc-tion of cardiac patches for the treatment of myocardial infarction. |
| Volume |
29 |
