title: MiR-136 modulates glioma cell sensitivity to temozolomide by targeting astrocyte elevated gene-1.
abstract: BACKGROUND
  Recent studies have linked chemotherapy resistance to the altered expression of microRNAs (miRNAs). Thus, miRNA-based approaches to modulating sensitivity to temozolomide (TMZ) may overcome chemoresistance. The aim of the present study was to investigate whether miR-136 could modulates glioma cell sensitivity to TMZ.
  
  
  METHODS
  The proliferation of glioma U251 cell line was evaluated by MTT assay. The expression of astrocyte elevated gene-1 (AEG-1)was detected by real‑time polymerase chain reaction (RT-PCR)and Western blot. The luciferase reporter gene was used to test whether AEG-1 was the target of the miR-136.
  
  
  RESULTS
  The MTT assay showed that U251 cells with miR-136 overexpression were significantly more sensitive to the therapy of TMZ than control cells. Luciferase assays revealed that miR-136 directly targeted the 3'UTR of AEG-1. qRT-PCR and western blotting analysis found that AEG-1 expression at the mRNA and protein levels decreased in the miR-136 mimic-treatment group relative to control group. Downregulation of AEG-1 expression by siRNAs, U251 cells became more sensitive to the therapy of TMZ. In addition, the enhanced growth-inhibitory effect by the miR-136 mimics transfection was enhanced after the addition of AEG-1 siRNA.
  
  
  CONCLUSIONS
  The present study provides the first evidence that miR-136 plays a key role in TMZ resistance by targeting the AEG-1 protein in glioma cell line, suggesting that miR-136 can be used to predict a patient's response to TMZ therapy as well as serve as a novel potential maker for glioma therapy.
  The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_173.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Cai
authors.forename: Yu-dan
authors.initials: YD
authors.lastname: Chen
authors.forename: Fan
authors.initials: F
authors.lastname: Liao
authors.affiliation: Department of Neurosurgery, The Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Hexi Yuelu District, Changsha 400013, Hunan, China. dr_wangzhifei@126.com.
authors.forename: Zhi-fei
authors.initials: ZF
authors.lastname: Wang
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001253:Astrocytes; D015815:Cell Adhesion Molecules / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins; D060888:Real-Time Polymerase Chain Reaction; D000077204:Temozolomide; D014162:Transfection
chemical_list: D018906:Antineoplastic Agents, Alkylating; D015815:Cell Adhesion Molecules; C577037:MIRN136 microRNA, human; C483039:MTDH protein, human; D008565:Membrane Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D003606:Dacarbazine; D000077204:Temozolomide