title: MicroRNA-125b-2 confers human glioblastoma stem cells resistance to             temozolomide through the mitochondrial pathway of apoptosis.
abstract: MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate protein             expression by cleaving or repressing the translation of target mRNAs. miR-125b,             one of the neuronal miRNAs, was recently found to be necessary for stem cell fission             and for making stem cells insensitive to chemotherapy signals. Temozolomide (TMZ)             is a promising chemotherapeutic agent for treating glioblastomas. However, resistance             develops quickly and with a high frequency. Given the insensitivity of some glioblastomas             to TMZ and the hypothesis that glioma stem cells cause resistance to drug therapy,             exploring the functions and mechanisms of miR-125b action on TMZ-treated glioblastoma             stem cells would be valuable. In this study, we found that miR-125b-2 is overexpressed             in glioblastoma multiforme tissues and the corresponding stem cells (GBMSC); downregulation             of miR-125b-2 expression in GBMSC could allow TMZ to induce GBMSC apoptosis. Additionally,             the expression of the anti-apoptotic protein Bcl-2 was decreased after the TMZ+miR-125b-2             inhibitor treatment, while the expression of the proapoptotic protein Bax was             increased. Further research demonstrated that the induction of apoptosis in GBMSC             is also associated with increased cytochrome c release from mitochondria, induction             of Apaf-1, activation of caspase-3 and poly-ADP-ribose polymerase (PARP). Taken             together, these results suggest that miR-125b-2 overexpression might confer glioblastoma             stem cells resistance to TMZ.
authors: Department of Neurosurgery, The First People's Hospital of Kunshan affiliated with Jiangsu University, Suzhou 15300, P.R. China. shileigff@126.com
authors: Lei
authors: L
authors: Shi
authors: Shuguang
authors: S
authors: Zhang
authors: Kun
authors: K
authors: Feng
authors: Furong
authors: F
authors: Wu
authors: Yi
authors: Y
authors: Wan
authors: Zhimin
authors: Z
authors: Wang
authors: Junxia
authors: J
authors: Zhang
authors: Yinyi
authors: Y
authors: Wang
authors: Wei
authors: W
authors: Yan
authors: Zhen
authors: Z
authors: Fu
authors: Yongping
authors: Y
authors: You
mesh_terms: D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D045304:Cytochromes c / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D000077204:Temozolomide; D014407:Tumor Cells, Cultured
chemical_list: D018906:Antineoplastic Agents, Alkylating; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D003606:Dacarbazine; D045304:Cytochromes c; D000077204:Temozolomide