title: MiR-145 expression accelerates esophageal adenocarcinoma progression by enhancing cell invasion and anoikis resistance.
abstract: BACKGROUND
  Carcinoma of the esophagus has a high case fatality ratio and is now the 6th most common cause of cancer deaths in the world. We previously conducted a study to profile the expression of miRNAs in esophageal adenocarcinoma (EAC) pre and post induction therapy. Of the miRNAs differentially expressed post induction chemoradiation, miR-145, a known tumor suppressor miRNA, was upregulated 8-fold following induction therapy, however, its expression was associated with shorter disease-free survival. This unexpected result was explored in this current study.
  
  
  METHODS
  In order to study the role of miR-145 in EAC, miRNA-145 was overexpressed in 3 EAC cell lines (OE33, FLO-1, SK-GT-4) and one ESCC cell line (KYSE-410). After validation of the expression of miR-145, hallmarks of cancer such as cell proliferation, resistance to chemotherapy drugs or anoikis, and cell invasion were analyzed.
  
  
  RESULTS
  There were no differences in cell proliferation and 5 FU resistance between miR145 cell lines and the control cell lines. miR-145 expression also had no effect on cisplatin resistance in two of three cell lines (OE33 and FLO-1), but miR-145 appeared to protect SK-GT-4 cells against cisplatin treatment. However, there was a significant difference in cell invasion, cell adhesion and resistance to anoikis. All three EAC miR-145 cell lines invaded more than their respective controls. Similarly, OE33 and SK-GT-4 miR-145 cell lines were able to survive longer in a suspension state.
  
  
  CONCLUSIONS
  While expression of miR-145 in ESCC stopped proliferation and invasion, expression of miR-145 in EAC cells enhanced invasion and anoikis resistance. Although more work is required to understand how miR-145 conveys these effects, expression of miR-145 appears to promote EAC progression by enhancing invasion and protection against anoikis, which could in turn facilitate distant metastasis.
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto Discovery Medical Tower, University Health Network, Toronto, Ontario, Canada.
authors.forename: Mathieu Francois
authors.initials: MF
authors.lastname: Derouet
authors.affiliation: Department of Medical Oncology, Princess Margaret Hospital, University Health Network Toronto, Ontario, Canada.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Liu
authors.affiliation: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Gail Elizabeth
authors.initials: GE
authors.lastname: Darling
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D023102:Anoikis / Q000187:drug effects / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004938:Esophageal Neoplasms / Q000473:pathology*; D005353:Fibronectins / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis
chemical_list: D005353:Fibronectins; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D005472:Fluorouracil