title: MicroRNA-181a promotes tumor growth and liver metastasis in colorectal cancer by targeting the tumor suppressor WIF-1.
abstract: BACKGROUND
  Given the emerging role of microRNA in tumor disease progression, we investigated the association between microRNA expression, liver metastasis and prognosis of colorectal cancer.
  
  
  METHODS
  Colorectal cancer tissues from patients with or without liver metastases were profiled to identify differentially expressed microRNA. Expression profile was further assessed using quantitative reverse transcription PCR and in situ hybridization. Correlation between miR-181a expression, the most differentially expressed microRNA, between patients with and without liver metastasis, and its downstream target genes were investigated using qRT-PCR. Luciferase reporter assay was conducted to establish functional association between miR-181a and its target genes. Manipulation of miR-181a expression and its consequences in tumor growth and metastasis were demonstrated in various in vitro and in vivo models.
  
  
  RESULTS
  miR-181a was revealed being the most elevated in CRC with liver metastases. miR-181a expression correlated with advanced stage, distant metastasis, and served as an independent prognostic factor of poor overall survival. Stable transfection of CRC cell lines with miR-181a promoted cell motility and invasion, as well as tumor growth and liver metastasis,while silencing its expression resulted in reduced migration and invasion. Additionally, we identified WIF-1 as direct and functional targets of miR-181a. Ectopic expression of miR-181a suppressed the epithelial markers E-cadherin and β-catenin, while enhanced the mesenchymal markers vimentin.
  
  
  CONCLUSIONS
  Our data demonstrate that miR-181a expression is associated with CRC liver metastasis and survival. miR-181a has strong tumor-promoting effects through inhibiting the expression of WIF-1, and its potential role in promoting epithelial-mesenchymal transition.
authors.forename: Dengbo
authors.initials: D
authors.lastname: Ji
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Chen
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Tiancheng
authors.initials: T
authors.lastname: Zhan
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Yao
authors.forename: Zhiqian
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Xi
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Colorectal Surgery, Peking University Cancer Hospital & Institute, No, 52 Fucheng Rd,, Haidian District, Beijing 100142, China. zlguj@bjmu.edu.cn.
authors.forename: Jin
authors.initials: J
authors.lastname: Gu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D016019:Survival Analysis; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; C495270:CTNNB1 protein, human; D015820:Cadherins; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D014746:Vimentin; C485569:WIF1 protein, human; D051176:beta Catenin
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