title: miR-145 inhibits invasion of bladder cancer cells by targeting PAK1.
abstract: OBJECTIVE
  MicroRNAs play important roles in cancer. In many cancers, miR-145 acts as a tumor suppressor, and it is down-regulated in bladder cancer. In the present study, we explored the modulation of oncogenic gene PAK1 by miR-145 in bladder cancer.
  
  
  METHODS
  Expression of miR-145 was detected in bladder cancer tissues and cell lines by quantitative real-time polymerase chain reaction. Through the bioinformatics approach, PAK1 has been predicted to be a direct target of miR-145 and was confirmed by the PAK1 messenger RNA 3'-untranslated region luciferase activity assay. To investigate whether miR-145 regulates PAK1 expression, it was overexpressed in J82 and T24 bladder cancer cells. In 10 paired bladder normal and tumor tissues, we determined the relationship between miR-145 and PAK1 through quantitative real-time polymerase chain reaction and western blot. By using transwell invasion assay and western blotting analysis, we investigated the effects of miR-145 and PAK1 on bladder cancer cell invasion and expression of invasion marker genes.
  
  
  RESULTS
  The level of miR-145 decreases and PAK1 protein expression up-regulates in bladder cancer tissue, as compared with the paired normal bladder tissue. Moreover, miR-145 directly targets PAK1 in bladder cancer cells. The level of miR-145 negatively correlates with PAK1 protein expression in bladder cancer. In addition, PAK1 promotes invasion and enhances the expression and activity of MMP-9, whereas miR-145 inhibits bladder cancer cell invasion and expressions of PAK1 and MMP-9.
  
  
  CONCLUSIONS
  Our results indicate that miR-145 inhibits bladder cancer cell invasion, at least partly through targeting PAK1. Restoration or replacement of miR-145 could be an efficient approach to inhibit PAK1 and bladder cancer development in the tumor therapy.
authors: Department of Urology, The First Hospital of Xi׳an Jiaotong University, Xi׳an, Shaanxi, P.R. China; Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi׳an, Shaanxi, P.R. China.
authors: Bo
authors: B
authors: Kou
authors: Department of Urology, The First Hospital of Xi׳an Jiaotong University, Xi׳an, Shaanxi, P.R. China; Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi׳an, Shaanxi, P.R. China.
authors: Yang
authors: Y
authors: Gao
authors: Department of Urology, The First Hospital of Xi׳an Jiaotong University, Xi׳an, Shaanxi, P.R. China; Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi׳an, Shaanxi, P.R. China.
authors: Chong
authors: C
authors: Du
authors: Department of Urology, The First Hospital of Xi׳an Jiaotong University, Xi׳an, Shaanxi, P.R. China; Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi׳an, Shaanxi, P.R. China.
authors: Qi
authors: Q
authors: Shi
authors: Department of Urology, The First Hospital of Xi׳an Jiaotong University, Xi׳an, Shaanxi, P.R. China; Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi׳an, Shaanxi, P.R. China.
authors: Shan
authors: S
authors: Xu
authors: Department of Urology, The First Hospital of Xi׳an Jiaotong University, Xi׳an, Shaanxi, P.R. China.
authors: Chen-Qing
authors: CQ
authors: Wang
authors: Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi׳an, Shaanxi, P.R. China.
authors: Xinyang
authors: X
authors: Wang
authors: Department of Urology, The First Hospital of Xi׳an Jiaotong University, Xi׳an, Shaanxi, P.R. China; Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi׳an, Shaanxi, P.R. China.
authors: Dalin
authors: D
authors: He
authors: Department of Urology, The First Hospital of Xi׳an Jiaotong University, Xi׳an, Shaanxi, P.R. China; Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi׳an, Shaanxi, P.R. China. Electronic address: guopeng661@mail.xjtu.edu.cn.
authors: Peng
authors: P
authors: Guo
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000328:Adult; D000368:Aged; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D018613:Microscopy, Confocal; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D054462:p21-Activated Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; C515903:PAK1 protein, human; D054462:p21-Activated Kinases; D020780:Matrix Metalloproteinase 9
keywords: Bladder cancer; Invasion; MMP-9; PAK1; miR-145