Methylation mediated silencing of miR-23b expression and its role in glioma stem cells

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.

► It is the first time to report that miR-23b was silenced mediated by hypermethylation in GSCs. ► The expression level of miR-23b is lower in U87 GSCs when compared with parallel U87 cells. ► miR-23b induced U87 GSCs’ cell-cycle arrest and proliferation inhibition. ► miR-23b enhances the sensitivity of U87 GSCs to TMZ.