title: Identification of crucial microRNAs and genes in hypoxia-induced human lung adenocarcinoma cells.
abstract: BACKGROUND
  Variations of microRNA (miRNA) expression profile in hypoxic lung cancer cells have not been studied so far. Therefore, using miRNA microarray technology, this study aimed to study the miRNA expression profile and investigate the potential crucial miRNAs and their target genes in hypoxia-induced human lung adenocarcinoma cells.
  
  
  METHODS
  Based on miRNA microarray, miRNA expression profiling of hypoxia-induced lung adenocarcinoma A549 cells was obtained. After identification of differentially expressed miRNAs (DE-miRNAs) in hypoxic cells, target genes of DE-miRNAs were predicted, and functional enrichment analysis of targets was conducted. Furthermore, the expression levels of DE-miRNAs and their target genes were validated by real-time quantitative polymerase chain reaction. In addition, using miRNA mimics, the effect of overexpressed DE-miRNAs on A549 cell behaviors (cell proliferation, cell cycle, and apoptosis) was evaluated.
  
  
  RESULTS
  In total, 14 DE-miRNAs (nine upregulated miRNAs and five downregulated miRNAs) were identified in hypoxic cells, compared with normoxic cells. Target genes of both upregulated and downregulated miRNAs were enriched in the functions such as chromatin modification, and pathways such as Wnt signaling pathway and transforming growth factor (TGF)-β signaling pathway. The expression levels of several miRNAs and their target genes were confirmed, including hsa-miR-301b/FOXF2, hsa-miR-148b-3p/WNT10B, hsa-miR-769-5p/(SMAD2, ARID1A), and hsa-miR-622. Among them, hsa-miR-301b was verified to regulate FOXF2, and hsa-miR-769-5p was verified to modulate ARID1A. In addition, the overexpression of hsa-miR-301b and hsa-miR-769-5p significantly affected the cell cycle of A549 cells, but not cell proliferation and apoptosis.
  
  
  CONCLUSIONS
  miRNA expression profile was changed in hypoxia-induced lung cancer cells. Those validated miRNAs and genes may play crucial roles in the response of lung cancer cells to hypoxia.
authors.affiliation: Department of Respiratory.
authors.forename: Ying
authors.initials: Y
authors.lastname: Geng
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Harbin Medical University.
authors.forename: Lili
authors.initials: L
authors.lastname: Deng
authors.affiliation: Department of Respiratory.
authors.forename: Dongju
authors.initials: D
authors.lastname: Su
authors.affiliation: Department of Respiratory.
authors.forename: Jinling
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Respiratory, The First Hospital of Harbin.
authors.forename: Dongjie
authors.initials: D
authors.lastname: Ge
authors.affiliation: Department of Respiratory.
authors.forename: Yongxia
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of Emergency, The Second Affiliated Hospital of Harbin Medical University Harbin, Heilongjiang, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jing
keywords: A549; hsa-miR-301b; hsa-miR-769-5p; hypoxia; lung cancer; microarray