title: Hypoxia-induced miR-497 decreases glioma cell sensitivity to TMZ by inhibiting apoptosis.
abstract: Understanding the resistance of glioma cells to chemotherapy has been an enormous challenge. In particular, mechanisms by which tumor cells acquire resistance to chemotherapy under hypoxic conditions are not fully understood. In this study, we have found that miR-497 is overexpressed in glioma and that hypoxia can induce the expression of miR-497 at the transcriptional level by binding with the hypoxia response element in the promoter. Ectopic overexpression of miR-497 promotes chemotherapy resistance in glioma cells by targeting PDCD4, a tumor suppressor that is involved in apoptosis. In contrast, the inhibition of miR-497 enhances apoptosis and increases the sensitivity of glioma cells to TMZ. These results suggest that miR-497 is a potential molecular target for glioma therapy.
authors: The Affiliated First People's Hospital of Shanghai Jiaotong University, School of Medicine, China.
authors: Jin
authors: J
authors: Lan
authors: The Affiliated First People's Hospital of Shanghai Jiaotong University, School of Medicine, China.
authors: Yajun
authors: Y
authors: Xue
authors: The Affiliated First People's Hospital of Shanghai Jiaotong University, School of Medicine, China.
authors: Huairui
authors: H
authors: Chen
authors: The Affiliated First People's Hospital of Shanghai Jiaotong University, School of Medicine, China.
authors: Sanhu
authors: S
authors: Zhao
authors: The Affiliated First People's Hospital of Shanghai Jiaotong University, School of Medicine, China.
authors: Zhijian
authors: Z
authors: Wu
authors: The Affiliated First People's Hospital of Shanghai Jiaotong University, School of Medicine, China.
authors: Jun
authors: J
authors: Fang
authors: The Affiliated First People's Hospital of Shanghai Jiaotong University, School of Medicine, China.
authors: Cong
authors: C
authors: Han
authors: The Affiliated First People's Hospital of Shanghai Jiaotong University, School of Medicine, China.
authors: Meiqing
authors: M
authors: Lou
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002470:Cell Survival; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020218:Response Elements; D000077204:Temozolomide; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D018906:Antineoplastic Agents, Alkylating; D051017:Apoptosis Regulatory Proteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C559640:MIRN497 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Drug resistance; Glioma; PDCD4; miR-497