title: miR-29c contribute to glioma cells temozolomide sensitivity by targeting O6-methylguanine-DNA methyltransferases indirectely.
abstract: Temozolomide (TMZ) is the most commonly used alkylating agent in glioma chemotherapy. However growing resistance to TMZ remains a major challenge to clinicians. The DNA repair protein O6-methylguanine-DNA methytransferase (MGMT) plays critical roles in TMZ resistance. Promoter methylation can inhibit MGMT expression and increase chemosensitivity. Here, we described a novel mechanism regulating MGMT expression. We showed that miR-29c suppressed MGMT expression indirectly via targeting specificity protein 1 (Sp1). MiR-29c overexpression increased TMZ efficacy in cultured glioma cells and in mouse xenograft models. The miR-29c levels were positively correlated with patient outcomes. Our data suggest miR-29c may be potential therapeutic targets for glioma treatment.
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guanzhou, Guangdong, China.
authors.forename: Songhua
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Department of Hypertension and Vascular Disease, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Xingsheng
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guanzhou, Guangdong, China.
authors.forename: Ruiyan
authors.initials: R
authors.lastname: Lv
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guanzhou, Guangdong, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D004260:DNA Repair; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D009368:Neoplasm Transplantation; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D000477:Alkylating Agents; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D003606:Dacarbazine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide
keywords: MGMT; TMZ; chemoresistance; glioblastoma; miR-29c