title: miR-146a functions as a tumor suppressor in prostate cancer by targeting Rac1.
abstract: BACKGROUND
  miR-146a (miR-146a-5p) has been reported to be aberrantly expressed in different types of cancers, the current knowledge about the role of miR-146a in prostate cancer is still limited.
  
  
  METHODS
  The expression levels of miR-146a in cell lines and tissues were measured by qRT-PCR and in situ hybridization. Effects of miR-146a on cell growth and migration were evaluated by colony formation assay and RTCA assay, respectively. The dual luciferase assay was used to examine the binding between miR-146a and the 3'UTR of potential targets.
  
  
  RESULTS
  We found that enforced over-expression of miR-146a in prostate cancer cells suppressed whereas knockdown of miR-146a increased anchorage-independent growth, migration, and invasion. Mechanistic studies revealed that miR-146a repressed the expression of Rac1 through binding to its 3'UTR. Consistently, knockdown of Rac1 phenocopied the anti-migration effect of overexpressing miR-146a, and knockdown of Rac1 in miR-146a-silencing cells antagonized the increase in cell motility induced by silencing miR-146a. Furthermore, miR-146a was found to be inversely correlated with Rac1 in human prostate cancer tissues.
  
  
  CONCLUSIONS
  Our data suggest that miR-146a plays a suppressive role in prostate cancer through down-regulation of Rac1. The miR-146a/Rac1 signaling axis may be a potential therapeutic target to prevent prostate cancer progression.
authors.affiliation: Department of Oncology, No. 3 People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Sun
authors.forename: Xian
authors.initials: X
authors.lastname: Zhao
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Yanli
authors.initials: Y
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.forename: Bing
authors.initials: B
authors.lastname: Jiang
authors.forename: Qin
authors.initials: Q
authors.lastname: Chen
authors.forename: Jianxiu
authors.initials: J
authors.lastname: Yu
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000502:physiology*
chemical_list: C542542:MIRN146 microRNA, human; D035683:MicroRNAs; C107953:RAC1 protein, human; D034741:RNA, Small Interfering; D020830:rac1 GTP-Binding Protein
keywords: Rac1; miR-146a; prostate cancer; tumor metastasis