Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
School of Interdisciplinary Informatics, University of Nebraska-Omaha, Omaha, NE, USA.
Cell Death Dis. 2014 Jan 9;5(1):e982. doi: 10.1038/cddis.2013.498.
Regulation of cellular proliferation and differentiation during brain development results from processes requiring several regulatory networks to function in synchrony. MicroRNAs are part of this regulatory system. Although many microRNAs are evolutionarily conserved, recent evolution of such regulatory molecules can enable the acquisition of new means of attaining specialized functions. Here we identify and report the novel expression and functions of a human and higher primate-specific microRNA, miR-1290, in neurons. Using human fetal-derived neural progenitors, SH-SY5Y neuroblastoma cell line and H9-ESC-derived neural progenitors (H9-NPC), we found miR-1290 to be upregulated during neuronal differentiation, using microarray, northern blotting and qRT-PCR. We then conducted knockdown and overexpression experiments to look at the functional consequences of perturbed miR-1290 levels. Knockdown of miR-1290 inhibited differentiation and induced proliferation in differentiated neurons; correspondingly, miR-1290 overexpression in progenitors led to a slowing down of the cell cycle and differentiation to neuronal phenotypes. Consequently, we identified that crucial cell cycle proteins were aberrantly changed in expression level. Therefore, we conclude that miR-1290 is required for maintaining neurons in a differentiated state.
在大脑发育过程中，细胞增殖和分化的调节来自于需要几个调节网络同步运作的过程。microRNAs 是这个调节系统的一部分。尽管许多 microRNAs 在进化上是保守的，但这些调节分子的最近进化可以使它们获得获得专门功能的新手段。在这里，我们鉴定并报告了一种新型的人类和高等灵长类动物特异性 microRNA，miR-1290，在神经元中的表达和功能。使用人胎源性神经祖细胞、SH-SY5Y 神经母细胞瘤细胞系和 H9-ESC 源性神经祖细胞（H9-NPC），我们发现 miR-1290 在神经元分化过程中上调，使用微阵列、Northern 印迹和 qRT-PCR。然后，我们进行了敲低和过表达实验，观察 miR-1290 水平失调的功能后果。miR-1290 的敲低抑制了分化神经元的分化，并诱导其增殖；相应地，祖细胞中 miR-1290 的过表达导致细胞周期减慢，并向神经元表型分化。因此，我们鉴定出关键的细胞周期蛋白的表达水平异常改变。因此，我们得出结论，miR-1290 是维持神经元分化状态所必需的。
