RNA-seq profiles of rat cardiomyocytes overexpressing hsa-miR-106b-5p, hsa-miR-93-5p, hsa-miR-25-3p or cel-miR-67

Myocardial regeneration is restricted to early postnatal life, when mammalian cardiomyocytes still retain the ability to proliferate. The molecular cues that induce cell cycle arrest of neonatal cardiomyocytes towards terminally differentiated adult heart muscle cells remain obscure. We report that the miR-106b~25cluster is higher expressed in the early postnatal myocardium and decreases in expression towards adulthood, especially under conditions of overload, and orchestrates the transition of cardiomyocyte hyperplasia towards cell cycle arrest and hypertrophy by virtue of its targetome. To identify the relevant targets of individual miRNAs in the miR-106b~15 cluster and elucidate the molecular mechanisms underlying the proliferative effects of this microRNA cluster, we assessed the global transcriptomic changes by deep-sequencing total neonatal mouse cardiomyocyte RNA after exogeneous transfection with hsa-miR-106b-5p, hsa-miR-93-5p, hsa-miR-25-3p and compared the transcriptomic profiles to cardiomyocytes transfected with cel-miR-67, a control miRNA.心肌再生仅局限于出生后早期阶段，此时哺乳动物心肌细胞仍保有增殖能力。介导新生心肌细胞向终末分化的成熟心肌细胞发生细胞周期阻滞的分子机制仍不明确。本研究发现，miR-106b~25 基因簇（miR-106b~25 cluster）在出生后早期心肌组织中呈高表达状态，随发育至成年阶段其表达水平逐渐下调，在负荷过载条件下该下调趋势尤为显著；该基因簇可通过其靶标组（targetome）调控心肌细胞从增殖增生向细胞周期阻滞与肥大的转变过程。为鉴定 miR-106b~15 基因簇中各 microRNA（miRNA）的关键靶标，并阐明该 microRNA 簇调控细胞增殖的分子机制，我们对外源转染了 hsa-miR-106b-5p、hsa-miR-93-5p 及 hsa-miR-25-3p 的新生小鼠心肌细胞总RNA进行深度测序以分析其全转录组变化，并将该转录组谱与转染了对照 microRNA（miRNA）cel-miR-67 的心肌细胞进行对比。