title: MiR-200a regulates epithelial to mesenchymal transition-related gene expression and determines prognosis in colorectal cancer patients.
abstract: BACKGROUND
  MicroRNAs (miRNAs) regulate the biological properties of colorectal cancer (CRC) cells and might serve as potential prognostic factors and therapeutic targets. In this study, we therefore globally profiled miRNAs associated with E-cadherin expression in CRC cells in an attempt to identify miRNAs that are associated with aggressive clinical course in CRC patients.
  
  
  METHODS
  Two CRC cell lines (Caco-2 and HRT-18) with different E-cadherin expression pattern were profiled for differences in abundance for more than 1000 human miRNAs using microarray technology. One of the most differentially expressed miRNAs, miR-200a was evaluated for its prognostic role in a cohort of 111 patients and independently validated in 217 patients of the Cancer Genome Atlas data set. To further characterise the biological role of miR-200a expression in CRC, in vitro miR-200a inhibition and overexpression were performed and the effects on cellular growth, apoptosis and epithelial-mesenchymal transition (EMT)-related gene expression were explored.
  
  
  RESULTS
  In situ hybridisation specifically localised miR-200a in CRC cells. In both cohorts, a low miR-200a expression was associated with poor survival (P<0.05). Multivariate Cox regression analysis identified low levels of miR-200a expression as an independent prognostic factor with respect to cancer-specific survival (HR=2.04, CI=1.28-3.25, P<0.002). Gain and loss of function assays for miR-200a in vitro led to a significantly differential and converse expression of EMT-related genes (P<0.001.) A low expression of miR-200a was also observed in cancer stem cell-enriched spheroid growth conditions (P<0.05).
  
  
  CONCLUSIONS
  In conclusion, our data suggest that low miR-200a expression is associated with poor prognosis in CRC patients. MiR-200a has a regulatory effect on EMT and is associated with cancer stem cell properties in CRC.
authors: 1] Division of Oncology, Department of Internal Medicine, Medical University of Graz (MUG), Graz, Austria [2] Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: M
authors: M
authors: Pichler
authors: Division of Oncology, Department of Internal Medicine, Medical University of Graz (MUG), Graz, Austria.
authors: A L
authors: AL
authors: Ress
authors: Institute of Pathology, Medical University of Graz (MUG), Graz, Austria.
authors: E
authors: E
authors: Winter
authors: Division of Oncology, Department of Internal Medicine, Medical University of Graz (MUG), Graz, Austria.
authors: V
authors: V
authors: Stiegelbauer
authors: RNA Biology Group, Institute of Genomic and Bioinformatics, Graz University of Technology, Graz, Austria.
authors: M
authors: M
authors: Karbiener
authors: Division of Oncology, Department of Internal Medicine, Medical University of Graz (MUG), Graz, Austria.
authors: D
authors: D
authors: Schwarzenbacher
authors: RNA Biology Group, Institute of Genomic and Bioinformatics, Graz University of Technology, Graz, Austria.
authors: M
authors: M
authors: Scheideler
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: C
authors: C
authors: Ivan
authors: Institute of Pathology, Medical University of Graz (MUG), Graz, Austria.
authors: S W
authors: SW
authors: Jahn
authors: 1] Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg, Austria [2] Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria.
authors: T
authors: T
authors: Kiesslich
authors: Division of Oncology, Department of Internal Medicine, Medical University of Graz (MUG), Graz, Austria.
authors: A
authors: A
authors: Gerger
authors: Division of Oncology, Department of Internal Medicine, Medical University of Graz (MUG), Graz, Austria.
authors: T
authors: T
authors: Bauernhofer
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: G A
authors: GA
authors: Calin
authors: Institute of Pathology, Medical University of Graz (MUG), Graz, Austria.
authors: G
authors: G
authors: Hoefler
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000235:genetics; D018938:Caco-2 Cells; D048708:Cell Growth Processes / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012189:Retrospective Studies; D014162:Transfection
chemical_list: C533896:MIRN200 microRNA, human; D035683:MicroRNAs