title: MiR-99a exerts anti-metastasis through inhibiting myotubularin-related protein 3 expression in oral cancer.
abstract: OBJECTIVE
  We aimed at studying the role of the most deregulated miR-99a, identifying its downstream targets, and exploring the clinical potential of miR-99a and its target(s) in oral cancer.
  
  
  METHODS
  Following confirmation of miR-99a deregulation in nine oral lines and 26 pairwise clinical specimens, miR-99a-manipulated oral cancer cells were subjected to cell proliferation, migration, invasion, and in vivo murine metastasis assays. We characterized putative miR-99a target(s) using luciferase reporter assays and genetic manipulation. The inverse relation of miR-99a and its target(s) was examined in clinical specimens using real-time PCR and Western blot analysis.
  
  
  RESULTS
  MiR-99a down-regulation was confirmed both in tested oral cancer cell lines and clinical specimens. Ectopic miR-99a expression inhibited oral cancer cell migration and invasion. Anti-miR-99a, silencing miR-99a functions, had the opposite effect. Myotubularin-related protein 3 (MTMR3) with one evolutionarily conserved seed region in the 3'-untranslated region was a novel miR-99a target. Depleting MTMR3 expression significantly reduced cell proliferation, migration, or invasion. There was an inverse expression of miR-99a and MTMR3 protein in oral cancer lines and clinical specimens.
  
  
  CONCLUSIONS
  miR-99a repressed oral cancer cell migration and invasion partly through decreasing MTMR3 expression. MTMR3 may serve as a therapeutic target for oral cancer treatment.
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Kuo
authors.forename: Y H
authors.initials: YH
authors.lastname: Tai
authors.forename: H I
authors.initials: HI
authors.lastname: Lo
authors.forename: Y L
authors.initials: YL
authors.lastname: Chen
authors.forename: H C
authors.initials: HC
authors.lastname: Cheng
authors.forename: W Y
authors.initials: WY
authors.lastname: Fang
authors.forename: S H
authors.initials: SH
authors.lastname: Lin
authors.forename: C L
authors.initials: CL
authors.lastname: Yang
authors.forename: S T
authors.initials: ST
authors.lastname: Tsai
authors.forename: L W
authors.initials: LW
authors.lastname: Wu
mesh_terms: D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology*; D009362:Neoplasm Metastasis; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
chemical_list: C561679:MIRN99 microRNA, human; D035683:MicroRNAs; C444436:MTMR3 protein, human; D054558:Protein Tyrosine Phosphatases, Non-Receptor
keywords: MTMR3; miR-99a; microRNA; oral cancer; phosphatase