Abstract：
In mammal, the myocardium loss cannot be recovered spontaneously due to the negligible proliferation ability of mature mammalian cardiomyocyte. However, accumulated evidence has shown that terminally differentiated mammalian cardiomyocyte also has proliferation potency, which can be mediated by several mechanisms. Here, we reported that circNCX1, the most abundant circular RNA in mammalian hearts, can affect the proliferation of murine cardiomyocytes. The level of circNCX1 is significantly elevated during heart development. Forced expression of circNCX1 inhibits cardiomyocyte proliferation, while silencing of endogenous circNCX1 in cardiomyocyte shows reversed effect in vitro. Mechanistically, circNCX1 functions via negatively regulating transcription activator BRG1. It bridges BRG1 and FBXW7 to enhance the ubiquitination and degradation of BRG1, decreasing the expression of BMP10 to lead cell cycle arrest. In summary, our study first revealed that circNCX1 is a modulator of cardiomyocyte proliferation.
摘要：
在哺乳动物中,由于成熟的哺乳动物心肌细胞的增殖能力可忽略不计，心肌损失不能自发恢复。然而,积累的证据表明，终末分化的哺乳动物心肌细胞也具有增殖潜能，这可以通过几种机制介导。这里,我们报道了哺乳动物心脏中最丰富的环状RNAcircNCX1，可以影响小鼠心肌细胞的增殖。circNCX1的水平在心脏发育过程中显著升高。circNCX1的强制表达抑制心肌细胞增殖，而内源性circNCX1在心肌细胞中的沉默在体外显示出逆转作用。机械上,circNCX1通过负调控转录激活因子BRG1起作用。它桥接BRG1和FBXW7以增强BRG1的泛素化和降解，降低BMP10的表达以导致细胞周期停滞。总之,我们的研究首次揭示circNCX1是心肌细胞增殖的调节剂。
