Nakajima Norio, Takahashi Tomosaburo, Kitamura Ryoji, Isodono Koji, Asada Satoshi, Ueyama Tomomi, Matsubara Hiroaki, Oh Hidemasa
Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Biochem Biophys Res Commun. 2006 Dec 1;350(4):1006-12. doi: 10.1016/j.bbrc.2006.09.153. Epub 2006 Oct 6.
MicroRNAs (miRNAs) are small non-coding RNAs emerging as important post-transcriptional gene regulators. In this study, we examined the role of miR-1, an miRNA specifically expressed in cardiac and skeletal muscle tissue, on the myogenic, osteoblastic, and adipogenic differentiation of C2C12 cells. Upon induction of myogenic differentiation, miR-1 was robustly expressed. Retrovirus-mediated overexpression of miR-1 markedly enhanced expression of muscle creatine kinase, sarcomeric myosin, and alpha-actinin, while the effects on myogenin and MyoD expression were modest. Formation of myotubes was significantly augmented in miR-1-overexpressing cells, indicating miR-1 expression enhanced not only myogenic differentiation but also maturation into myotubes. In contrast, osteoblastic and adipogenic differentiation was not affected by forced expression of miR-1. Thus, the muscle-specific miRNA, miR-1, plays important roles in controlling myogenic differentiation and maturation in lineage-committed cells, rather than functioning in fate determination.
微小RNA(miRNA)是一类小型非编码RNA,逐渐成为重要的转录后基因调节因子。在本研究中,我们检测了miR-1(一种在心肌和骨骼肌组织中特异性表达的miRNA)对C2C12细胞成肌、成骨和成脂分化的作用。在诱导成肌分化时,miR-1表达强烈。逆转录病毒介导的miR-1过表达显著增强了肌肉肌酸激酶、肌节肌球蛋白和α-辅肌动蛋白的表达,而对生肌调节因子和肌分化抗原表达的影响较小。在过表达miR-1的细胞中,肌管形成显著增加,表明miR-1表达不仅增强了成肌分化,还促进了其向肌管的成熟。相反,成骨和成脂分化不受miR-1强制表达的影响。因此,肌肉特异性miRNA miR-1在控制定向分化细胞的成肌分化和成熟中发挥重要作用,而不是在命运决定中起作用。