title: MiR-451 inhibits cell growth and invasion by targeting MIF and is associated with survival in nasopharyngeal carcinoma.
abstract: BACKGROUND
  MiRNAs play important roles in diverse biological processes including tumorigenesis. However, little is known about the function and mechanism of miR-451 in nasopharyngeal carcinoma (NPC).
  
  
  METHODS
  Quantitative RT-PCR was used to quantify miR-451 expression in NPC cell lines and clinical tissues. Kaplan-Meier curves were used to estimate the association between miR-451 expression and survival. The MTT, colony formation, Transwell migration and invasion assays, and a xenograft model were performed. A miR-451 target was confirmed using luciferase reporter assays, quantitative RT-PCR, and Western blotting.
  
  
  RESULTS
  MiR-451 was significantly downregulated in NPC cell lines and clinical tissues (P < 0.01). Patients with low expression of miR-451 had poorer overall survival (HR, 1.98; 95% CI, 1.16-3.34; P = 0.01) and disease-free survival (HR, 1.68; 95% CI, 1.07-2.62; P = 0.02) than patients with high expression. MiR-451 was an independent prognostic factor in NPC in multivariate Cox regression analysis. Ectopic expression of miR-451 suppressed cell viability, colony formation, and cell migration and invasion in vitro, and inhibited xenograft tumor growth in vivo. MIF was verified as a direct target of miR-451, and MIF regulated NPC cell growth and invasion.
  
  
  CONCLUSIONS
  The newly identified miR-451/MIF pathway provides insight into NPC initiation and progression, and may represent a novel therapeutic target.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.forename: Ning
authors.initials: N
authors.lastname: Jiang
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Qing-Mei
authors.initials: QM
authors.lastname: He
authors.forename: Ya-Fei
authors.initials: YF
authors.lastname: Xu
authors.forename: Ying-Qin
authors.initials: YQ
authors.lastname: Li
authors.forename: Ling-Long
authors.initials: LL
authors.lastname: Tang
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Mao
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou People's Republic of China. majun2@mail.sysu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
mesh_terms: D000328:Adult; D000818:Animals; D001483:Base Sequence; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D016016:Proportional Hazards Models; D034622:RNA Interference; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D047368:Tumor Burden
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C532045:MIRN29a microRNA, human; C531201:MIRN451 microRNA, human; D008263:Macrophage Migration-Inhibitory Factors; D035683:MicroRNAs; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C087334:TIAM1 protein, human; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human