title: Up-regulation of miR-497 confers resistance to temozolomide in human glioma cells by targeting mTOR/Bcl-2.
abstract: The occurrence of an inherent or acquired resistance to temozolomide (TMZ) is a major burden for patients suffering from glioma. Recently, studies have demonstrated that microRNAs play an important role in the regulation of tumor properties in cancers. However, whether miR-497 contributes to glioma resistance to chemotherapy is not fully understood. In this study, we showed that the expression of miR-497 was markedly up-regulated in TMZ-resistant glioma cells; high miR-497 expression level was associated with TMZ-resistant phenotype of glioma cells. The down-regulation of miR-497 in glioma cells enhanced the apoptosis-induction and growth inhibition effects of TMZ both in vitro and in vivo, whereas promotion of miR-497 increased the chemosensitization of glioma cells to TMZ. The increased level of miR-497 in TMZ-resistant glioma cells was concurrent with the up-regulation of insulin-like growth factor 1 receptor (IGF1R)/insulin receptor substrate 1 (IRS1) pathway-related proteins, that is, IGF1R, IRS1, mammalian target of rapamycin (mTOR), and Bcl-2. In addition, the knockdown of mTOR and Bcl-2 reduced the tolerance of glioma cells to TMZ. Our results demonstrated that overexpression of miR-497 is significantly correlated with TMZ resistance in glioma cells by regulating the IGF1R/IRS1 pathway. Therefore, miR-497 may be used as a new target for treatment of chemotherapy-resistant glioma.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Canglang District, Suzhou, Jiangsu, 215000, China.|Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
authors.forename: Danhua
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Tu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zeng
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Canglang District, Suzhou, Jiangsu, 215000, China.
authors.forename: Zhengquan
authors.initials: Z
authors.lastname: Yu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D017209:Apoptosis; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*; D000077204:Temozolomide; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D018906:Antineoplastic Agents, Alkylating; C000595707:BCL2 protein, human; C559640:MIRN497 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D003606:Dacarbazine; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D000077204:Temozolomide
keywords: IGF1R/IRS1 pathway; microRNA; proliferation; tumor biology