title: Hypoxia/lncRNA-AK123072/EGFR pathway induced metastasis and invasion in gastric cancer.
abstract: OBJECTIVE
  To investigate the role of long noncoding RNAs (lncRNAs) in hypoxia-induced gastric cancer (GC) metastasis and invasion.
  
  
  METHODS
  We investigated the differentially expressed lncRNAs resulting from hypoxia-induced GC and normoxia conditions using microarrays and validated our results through real-time quantitative polymerase chain reaction. The role of the targeting lncRNA was further detected by in vivo and in vitro assays.
  
  
  RESULTS
  We found an lncRNA, AK123072, which was up-regulated by hypoxia. AK123072 was frequently up-regulated in GC samples and promoted GC migration and invasion in vivo and in vitro. Furthermore, AK123072 could mediate the metastasis of hypoxia-induced GC cells. Next, we identified EGFR, which was a metastasis-related gene regulated by AK123072. In addition, we found that the expression of EGFR was positively correlated with that of AK123072 in the clinical GC samples used in our study. Furthermore, we found that the EGFR gene CpG island methylation was significantly increased in GC cells depleted of AK123072. Intriguingly, EGFR expression was also increased by hypoxia, and EGFR up-regulation by AK123072 mediated hypoxia-induced GC cell metastasis.
  
  
  CONCLUSIONS
  Our results identified hypoxia/lncRNA-AK123072/EGFR pathway in gastric cancer pathogenesis and this might help in the development of new therapeutics in clinics.
authors.affiliation: Department of Gastrointestinal Surgery, 1st Affiliated Hospital of Zhengzhou University Henan Province, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of General Surgery, 1st Renmin Hospital of Shangqiu Henan Province, China.
authors.forename: Ruoming
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Cancer, 1st Renmin Hospital of Shangqiu Henan Province, China.
authors.forename: Tengteng
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery, 1st Affiliated Hospital of Zhengzhou University Henan Province, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Dong
keywords: AK123702; EGFR; cancer gene therapy; gastric cancer (GC); hypoxia; invasion; long noncoding RNAs (lncRNAs); metastasis