title: MicroRNA-218 Increases the Sensitivity of Bladder Cancer to Cisplatin by Targeting Glut1.
abstract: OBJECTIVE
  MicroRNA-218 (miR-218) is down-regulated in many malignancies that have been implicated in the regulation of diverse processes in cancer cells. However, the involvement of miR-218 in chemo-sensitivity to cisplatin and the precise mechanism of this action remained unknown in bladder cancer.
  
  
  METHODS
  qRT-PCR was used to detect miR-218 and its target Glut1 expression in bladder cancer cell lines T24 and EJ. CCK-8 method was utilized to measure the cell viability. IC 50 was calculated via a probit regression model. Glut1 was detected by western blotting for analysis of potential mechanism. Luciferase reporter assay was utilized to validate Glut1 as a direct target gene of miR-218. The intracellular level of GSH and ROS were determined using a commercial colorimetric assay kit and 2', 7'-dichlorodihydro-fluorescein diacetate, respectively.
  
  
  RESULTS
  Over-expression of miR-218 significantly reduced the rate of glucose uptake and total level of GSH and enhanced the chemo-sensitivity of bladder cancer to cisplatin. Mechanistically, Glut1 was found to be a direct and functional target of miR-218. Up-regulation of Glut1 could restore chemo-resistance in T24 and EJ cells. On the contrary, knockdown of Glut1 could generate a similar effect as up-regulating the expression of miR-218.
  
  
  CONCLUSIONS
  MiR-218 increases the sensitivity of bladder cancer to cisplatin by targeting Glut1. Restoration of miR-218 and repression of glut1 may provide a potential strategy to restore chemo-sensitivity in bladder cancer.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.forename: Yidong
authors.initials: Y
authors.lastname: Cheng
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhang
authors.forename: Chengdi
authors.initials: C
authors.lastname: Yang
authors.forename: Xiaheng
authors.initials: X
authors.lastname: Deng
authors.forename: Pengchao
authors.initials: P
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Tao
authors.forename: Haiwei
authors.initials: H
authors.lastname: Yang
authors.forename: Jifu
authors.initials: J
authors.lastname: Wei
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Tang
authors.forename: Wenbo
authors.initials: W
authors.lastname: Yuan
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lu
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Xu
authors.forename: Min
authors.initials: M
authors.lastname: Gu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D005947:Glucose / Q000037:antagonists & inhibitors / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005978:Glutathione / Q000819:agonists / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D051272:Glucose Transporter Type 1; C547471:MIRN218 microRNA, human; D035683:MicroRNAs; C495677:SLC2A1 protein, human; D008156:Luciferases; D005978:Glutathione; D005947:Glucose; D002945:Cisplatin
keywords: Bladder cancer; Chemo-sensitivity; Cisplatin; Glut1; MiR-218