Department of Neurosurgery, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi 214023, PR China.
Neurosci Lett. 2012 Oct 24;528(2):185-9. doi: 10.1016/j.neulet.2012.08.055. Epub 2012 Sep 5.
MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate gene expression at a post-transcriptional level. Some miRNAs harboring CGIs undergo methylation mediated silencing, a characteristic of many tumor suppressor genes. To identify such miRNAs in glioma stem cells (GSCs), we first showed that miR-23b is frequently methylated in GSCs but not in parallel U87 cells. Meanwhile, miR-23b expression was also markedly reduced in GSCs compared with matching U87 cells. Furthermore, treatment with 5-aza can increase miR-23b expression in GSCs. In addition, ectopic expression of miR-23b in GSCs induces cell cycle arrest and proliferation inhibition. Further analysis showed that miR-23b could enhance the sensitivity of U87 GSCs to TMZ. Our results suggest that miR-23b is epigenetically down-regulated and restoration of miR-23b can effectively suppress cell growth in GSCs.
微小 RNA（miRNAs）是一类小的非编码 RNA，在转录后水平上负调控基因表达。一些含有 CGIs 的 miRNAs 经历甲基化介导的沉默，这是许多肿瘤抑制基因的特征。为了在神经胶质瘤干细胞（GSCs）中鉴定此类 miRNAs，我们首先表明 miR-23b 在 GSCs 中经常发生甲基化，但在平行的 U87 细胞中则不然。同时，与匹配的 U87 细胞相比，GSCs 中 miR-23b 的表达也明显降低。此外，5-aza 处理可增加 GSCs 中 miR-23b 的表达。此外，在 GSCs 中外源性表达 miR-23b 可诱导细胞周期停滞和增殖抑制。进一步分析表明，miR-23b 可增强 U87 GSCs 对 TMZ 的敏感性。我们的结果表明，miR-23b 被表观遗传地下调，恢复 miR-23b 可有效抑制 GSCs 中的细胞生长。
