Hypoxia/lncRNA-AK123072/EGFR pathway induced metastasis and invasion in gastric cancer.

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.

CONCLUSION

Our results identified hypoxia/lncRNA-AK123072/EGFR pathway in gastric cancer pathogenesis and this might help in the development of new therapeutics in clinics.