Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China.
FEBS Lett. 2012 Nov 2;586(21):3831-9. doi: 10.1016/j.febslet.2012.08.023. Epub 2012 Sep 18.
microRNAs (miRNAs) play important role in regulating cancer stem cell self-renewal and differentiation, but the expression prolife of miRNAs in glioma stem cells (GSCs) has not been addressed. Here, we found that CD133 positive GSCs possess a unique miRNAs profile compared to CD133 negative glioblastoma cells. miR-125b, as one of neuronal miRNAs, is the most significantly down-regulated miRNAs and overexpression of miR-125b inhibits the proliferation of CD133 positive GSCs and reduces the expression of "stem" marker. Furthermore, two binding sites for miR-125b are identified in the 3'UTR of E2F2 and overexpression of miR-125b in CD133 positive GSCs represses the endogenous level of E2F2 protein. This study demonstrated that miR-125b plays important roles in regulating the proliferation of GSCs by directly targeting E2F2.
微小 RNA(miRNAs)在调节癌症干细胞自我更新和分化方面发挥着重要作用,但胶质瘤干细胞(GSCs)中 miRNAs 的表达谱尚未得到解决。在这里,我们发现 CD133 阳性 GSCs 与 CD133 阴性神经胶质瘤细胞相比具有独特的 miRNAs 谱。miR-125b 作为一种神经元 miRNAs,是下调最显著的 miRNAs,过表达 miR-125b 抑制 CD133 阳性 GSCs 的增殖,并降低“干细胞”标志物的表达。此外,在 E2F2 的 3'UTR 中鉴定出两个 miR-125b 的结合位点,CD133 阳性 GSCs 中转录的 miR-125b 抑制内源性 E2F2 蛋白的水平。本研究表明,miR-125b 通过直接靶向 E2F2 对 GSCs 的增殖起重要作用。