title: Intermittent hypoxia with or without hypercapnia is associated with tumorigenesis by decreasing the expression of brain derived neurotrophic factor and miR-34a in rats.
abstract: BACKGROUND
  Very recent studies revealed that obstructive sleep apnoea (OSA) is a contributor of the increased incidence and mortality of cancer in humans, but mechanisms of how OSA promotes tumorigenesis remains largely unknown. We investigated whether intermittent hypoxia with and without hypercapnia plays a role in tumorigenesis.
  
  
  METHODS
  First, Sprague-Dawley (SD) male rats (12 weeks old) were subjected to different hypoxia exposures: intermittent hypoxia and intermittent hypoxia with hypercapnia; continuous hypoxia and normal air. The systemic application of chronic fast rate hypoxia with or without hypercapnia mimicked severe OSA patients with apnoea/hypopnea index equivalent to 60 events per hour. Then routine blood tests were performed and the levels of brain derived neurotrophic factor (BDNF) and miR-34a were examined.
  
  
  RESULTS
  In contrast to intermittent hypoxia with hypercapnia, both intermittent hypoxia and continuous hypoxia treatments caused significantly higher levels of haematology parameters than normoxia treatments. Compared to normoxia, intermittent hypoxia with hypercapnia exposure resulted in substantial decrease of serum BDNF and, miR-34a in the lower brainstem, while less pronounced results were found in intermittent hypoxia and continuous hypoxia exposure.
  
  
  CONCLUSIONS
  The exposure of intermittent hypoxia with or without hypercapnia, mimicking the situations in severe OSA patients, was associated with, or even promoted tumorigenesis.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing 100034, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning 110042, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Respiratory Medicine, Peking University Shougang Hospital, Beijing 100041, China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing 100034, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing 100034, China. Email: wangguangfa@hotmail.com.
authors.forename: Guangfa
authors.initials: G
authors.lastname: Wang
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D006935:Hypercapnia / Q000097:blood / Q000150:complications*; D000860:Hypoxia / Q000097:blood / Q000150:complications*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C560944:MIRN34 microRNA, rat; D035683:MicroRNAs