title: MiR-193b promotes autophagy and non-apoptotic cell death in oesophageal cancer cells.
abstract: BACKGROUND
  Successful treatment of oesophageal cancer is hampered by recurrent drug resistant disease. We have previously demonstrated the importance of apoptosis and autophagy for the recovery of oesophageal cancer cells following drug treatment. When apoptosis (with autophagy) is induced, these cells are chemosensitive and will not recover following chemotherapy treatment. In contrast, when cancer cells exhibit only autophagy and limited Type II cell death, they are chemoresistant and recover following drug withdrawal.
  
  
  METHODS
  MicroRNA (miRNA) expression profiling of an oesophageal cancer cell line panel was used to identify miRNAs that were important in the regulation of apoptosis and autophagy. The effects of miRNA overexpression on cell death mechanisms and recovery were assessed in the chemoresistant (autophagy inducing) KYSE450 oesophageal cancer cells.
  
  
  RESULTS
  MiR-193b was the most differentially expressed miRNA between the chemosensitive and chemoresistant cell lines with higher expression in chemosensitive apoptosis inducing cell lines. Colony formation assays showed that overexpression of miR-193b significantly impedes the ability of KYSE450 cells to recover following 5-fluorouracil (5-FU) treatment. The critical mRNA targets of miR-193b are unknown but target prediction and siRNA data analysis suggest that it may mediate some of its effects through stathmin 1 regulation. Apoptosis was not involved in the enhanced cytotoxicity. Overexpression of miR-193b in these cells induced autophagic flux and non-apoptotic cell death.
  
  
  CONCLUSIONS
  These results highlight the importance of miR-193b in determining oesophageal cancer cell viability and demonstrate an enhancement of chemotoxicity that is independent of apoptosis induction.
authors.affiliation: Cork Cancer Research Centre, 4th Floor Western Gateway Building, University College Cork, Cork, Ireland. michellenyhan@yahoo.co.uk.
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Nyhan
authors.affiliation: Cork Cancer Research Centre, 4th Floor Western Gateway Building, University College Cork, Cork, Ireland. tracey.odonovan@ucc.ie.
authors.forename: Tracey R
authors.initials: TR
authors.lastname: O'Donovan
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands. a.boersma@erasmusmc.nl.
authors.forename: Antonius W M
authors.initials: AW
authors.lastname: Boersma
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands. e.wiemer@erasmusmc.nl.
authors.forename: Erik A C
authors.initials: EA
authors.lastname: Wiemer
authors.affiliation: Cork Cancer Research Centre, 4th Floor Western Gateway Building, University College Cork, Cork, Ireland. s.mckenna@ucc.ie.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: McKenna
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics*; D001343:Autophagy / Q000235:genetics*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism*; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C546818:MIRN193 microRNA, human; D035683:MicroRNAs; D005472:Fluorouracil