LSU Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Neurosci Lett. 2010 May 26;476(1):18-22. doi: 10.1016/j.neulet.2010.03.054. Epub 2010 Mar 27.
Micro RNAs (miRNAs) are post-transcriptional modulators of gene expression that regulate the stability and translation of their target messenger RNAs (mRNAs). Here we report that the levels of a human brain-enriched miRNA-125b are up-regulated in interleukin-6 (IL-6)-stressed normal human astrocytes (NHA), a treatment known to induce astrogliosis. In vitro, anti-miRNA-125b added exogenously to IL-6-stressed NHA cultures attenuated both glial cell proliferation and increased the expression of the cyclin-dependent kinase inhibitor 2A (CDKN2A), a miRNA-125b target and negative regulator of cell growth. A strong positive correlation between miRNA-125b abundance and the glial cell markers glial fibrillary acidic protein (GFAP) and vimentin, and CDKN2A down-regulation was noted in advanced Alzheimer's disease (AD) and in Down's syndrome (DS) brain, chronic neurological disorders associated with astrogliosis. The results suggest that miRNA-125b up-regulation contributes to astrogliosis and to defects in the cell cycle that are characteristic of degenerating brain tissues.
微小 RNA（miRNAs）是基因表达的转录后调节因子，可调节其靶信使 RNA（mRNA）的稳定性和翻译。在这里，我们报告说，白细胞介素 6（IL-6）应激下的正常人星形胶质细胞（NHA）中，一种已知可诱导星形胶质细胞增生的治疗方法，上调了富含人脑的 miRNA-125b 的水平。在体外，向 IL-6 应激的 NHA 培养物中添加外源性抗 miRNA-125b 可减弱神经胶质细胞增殖，并增加周期蛋白依赖性激酶抑制剂 2A（CDKN2A）的表达，miRNA-125b 的靶标和细胞生长的负调节剂。在晚期阿尔茨海默病（AD）和唐氏综合征（DS）大脑中，观察到 miRNA-125b 丰度与神经胶质细胞标志物胶质纤维酸性蛋白（GFAP）和波形蛋白以及 CDKN2A 下调之间存在很强的正相关，这是与星形胶质细胞增生和细胞周期缺陷相关的慢性神经退行性疾病退化脑组织的特征。结果表明，miRNA-125b 的上调有助于星形胶质细胞增生，并导致细胞周期缺陷，这是退化脑组织的特征。
