PMID- 28064447 OWN - NLM STAT- MEDLINE DCOM- 20171116 LR - 20220311 IS - 2045-7634 (Electronic) IS - 2045-7634 (Linking) VI - 6 IP - 2 DP - 2017 Feb TI - Up-regulation of miR-497 confers resistance to temozolomide in human glioma cells by targeting mTOR/Bcl-2. PG - 452-462 LID - 10.1002/cam4.987 [doi] AB - 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. CI - (c) 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. FAU - Zhu, Danhua AU - Zhu D AD - Department of Neurosurgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Canglang District, Suzhou, Jiangsu, 215000, China. AD - Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China. FAU - Tu, Ming AU - Tu M AD - Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China. FAU - Zeng, Bo AU - Zeng B AD - Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China. FAU - Cai, Lin AU - Cai L AD - Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China. FAU - Zheng, Weiming AU - Zheng W AD - Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China. FAU - Su, Zhipeng AU - Su Z AD - Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China. FAU - Yu, Zhengquan AU - Yu Z AD - Department of Neurosurgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Canglang District, Suzhou, Jiangsu, 215000, China. LA - eng PT - Journal Article DEP - 20170108 PL - United States TA - Cancer Med JT - Cancer medicine JID - 101595310 RN - 0 (3' Untranslated Regions) RN - 0 (Antineoplastic Agents, Alkylating) RN - 0 (BCL2 protein, human) RN - 0 (MIRN497 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 7GR28W0FJI (Dacarbazine) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - YF1K15M17Y (Temozolomide) SB - IM MH - 3' Untranslated Regions MH - Animals MH - Antineoplastic Agents, Alkylating/pharmacology MH - Apoptosis MH - Brain Neoplasms/*genetics/pathology MH - Cell Line, Tumor MH - Cell Proliferation MH - Dacarbazine/analogs & derivatives/pharmacology MH - *Drug Resistance, Neoplasm MH - Gene Expression Regulation, Neoplastic MH - Glioma/*genetics/pathology MH - Humans MH - Mice MH - MicroRNAs/*genetics MH - Proto-Oncogene Proteins c-bcl-2/*genetics MH - Signal Transduction MH - TOR Serine-Threonine Kinases/*genetics MH - Temozolomide MH - *Up-Regulation PMC - PMC5313645 OTO - NOTNLM OT - IGF1R/IRS1 pathway OT - microRNA OT - proliferation OT - tumor biology EDAT- 2017/01/09 06:00 MHDA- 2017/11/29 06:00 PMCR- 2017/01/08 CRDT- 2017/01/09 06:00 PHST- 2016/08/27 00:00 [received] PHST- 2016/10/27 00:00 [revised] PHST- 2016/11/07 00:00 [accepted] PHST- 2017/01/09 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] PHST- 2017/01/09 06:00 [entrez] PHST- 2017/01/08 00:00 [pmc-release] AID - CAM4987 [pii] AID - 10.1002/cam4.987 [doi] PST - ppublish SO - Cancer Med. 2017 Feb;6(2):452-462. doi: 10.1002/cam4.987. Epub 2017 Jan 8.