PDF(Pubmed)
Abstract：
Enhancing cardiomyocyte proliferation is essential to reverse or slow down the heart failure progression in many cardiovascular diseases such as myocardial infarction (MI). Long non-coding RNAs (lncRNAs) have been reported to regulate cardiomyocyte proliferation. In particular, lncRNA urothelial carcinoma-associated 1 (lncUCA1) played multiple roles in regulating cell cycle progression and cardiovascular diseases, making lncUCA1 a potential target for promoting cardiomyocyte proliferation. However, the role of lncUCA1 in cardiomyocyte proliferation remains unknown. This study aimed at exploring the function and underlying molecular mechanism of lncUCA1 in cardiomyocyte proliferation. Quantitative RT-PCR showed that lncUCA1 expression decreased in postnatal hearts. Gain-and-loss-of-function experiments showed that lncUCA1 positively regulated cardiomyocyte proliferation in vitro and in vivo. The bioinformatics program identified miR-128 as a potential target of lncUCA1, and loss of miR-128 was reported to promote cardiomyocyte proliferation by inhibiting the SUZ12/P27 pathway. Luciferase reporter assay, qRT-PCR, western blotting, and immunostaining experiments further revealed that lncUCA1 acted as a ceRNA of miR-128 to upregulate its target SUZ12 and downregulate P27, thereby increasing cyclin B1, cyclin E, CDK1 and CDK2 expression to promote cardiomyocyte proliferation. In conclusion, upregulation of lncRNA UCA1 promoted cardiomyocyte proliferation by inhibiting the miR-128/SUZ12/P27 pathway. Our results indicated that lncUCA1 might be a new therapeutic target for stimulating cardiomyocyte proliferation.
摘要：
在许多心血管疾病如心肌梗死(MI)中,增强心肌细胞增殖对于逆转或减缓心力衰竭进展是必需的。已经报道了长链非编码RNA(lncRNA)调节心肌细胞增殖。特别是,lncRNA尿路上皮癌相关1（lncUCA1）在调节细胞周期进程和心血管疾病中起着多重作用，使lncUCA1成为促进心肌细胞增殖的潜在靶标。然而,lncUCA1在心肌细胞增殖中的作用尚不清楚.本研究旨在探讨lncUCA1在心肌细胞增殖中的作用及其分子机制。定量RT-PCR显示lncUCA1在出生后心脏中的表达降低。功能的获得和丧失实验表明，lncUCA1在体外和体内都能正向调节心肌细胞的增殖。生物信息学程序将miR-128鉴定为lncUCA1的潜在靶标，并且据报道miR-128的缺失通过抑制SUZ12/P27途径促进心肌细胞增殖。荧光素酶报告基因测定，qRT-PCR,西方印迹,和免疫染色实验进一步显示，lncUCA1充当miR-128的ceRNA，上调其靶标SUZ12并下调P27，从而增加细胞周期蛋白B1，细胞周期蛋白E，CDK1和CDK2表达增进心肌细胞增殖。总之,lncRNAUCA1的上调通过抑制miR-128/SUZ12/P27途径促进心肌细胞增殖。我们的结果表明，lncUCA1可能是刺激心肌细胞增殖的新治疗靶标。
