title: Methylation mediated silencing of miR-23b expression and its role in glioma stem cells.
abstract: 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.
authors.affiliation: Department of Neurosurgery, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi 214023, PR China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Geng
authors.forename: Hui
authors.initials: H
authors.lastname: Luo
authors.forename: Yi
authors.initials: Y
authors.lastname: Pu
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Zhou
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wu
authors.forename: Wenhui
authors.initials: W
authors.lastname: Xu
authors.forename: Zhengxiang
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001932:Brain Neoplasms; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077209:Decitabine; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D005910:Glioma; D006801:Humans; D008745:Methylation; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D000077204:Temozolomide
chemical_list: D000970:Antineoplastic Agents; C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D000077209:Decitabine; D003606:Dacarbazine; D001374:Azacitidine; D000077204:Temozolomide