lncRNA BC005927 upregulates EPHB4 and promotes gastric cancer metastasis under hypoxia

Summary

Hypoxia plays a critical role in the metastasis of gastric cancer (GC), yet the underlying mechanism remains largely unclear. It is also not known if lncRNAs are involved in the contribution of hypoxia to the GC metastasis. In this study, we found that lncRNA BC005927 can be induced by hypoxia in GC cells and mediates hypoxia-induced GC cell metastasis. Furthermore, BC005927 is frequently up-regulated in GC samples and increased BC005927 expression was correlated with a higher tumor-node-metastasis stage. GC patients with higher BC005927 expression had poorer prognoses than those with lower expression. Additional experiments revealed that BC005927 expression is induced by HIF-1a, CHIP assay and luciferase reporter assays confirmed that this lncRNA is a direct transcriptional target of HIF-1a. Next, we found that EPHB4, a metastasis-related gene, is regulated by BC005927 and that the expression of EPHB4 was positively correlated with that of BC005927 in the clinical GC samples assessed. Intriguingly, EPHB4 expression was also increased under hypoxia, and its upregulation by BC005927 resulted in hypoxia-induced GC cell metastasis. These results advance the current understanding of the role of BC005927 in the regulation of hypoxia signaling and offer new avenues for the development of therapeutic interventions against cancer progression.

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