Long noncoding RNA BC 005927 upregulates EPHB 4 and promotes gastric cancer metastasis under hypoxia

Hypoxia plays a critical role in the metastasis of gastric cancer ( GC ), yet the underlying mechanism remains largely unclear. It is also not known whether long, noncoding RNA s (lnc RNA s) are involved in the contribution of hypoxia to GC metastasis. In the present study, we found that lnc RNA BC...

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Veröffentlicht in:Cancer science 2018-04, Vol.109 (4), p.988-1000
Hauptverfasser: Liu, Xiangqiang, Wang, Yafang, Sun, Li, Min, Jie, Liu, Jiaming, Chen, Di, Zhang, Hongbo, Zhang, Hongwei, Zhang, Helong, Zhou, Yongan, Liu, Lili
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Sprache:eng
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Zusammenfassung:Hypoxia plays a critical role in the metastasis of gastric cancer ( GC ), yet the underlying mechanism remains largely unclear. It is also not known whether long, noncoding RNA s (lnc RNA s) are involved in the contribution of hypoxia to GC metastasis. In the present study, we found that lnc RNA BC 005927 can be induced by hypoxia in GC cells and mediates hypoxia‐induced GC cell metastasis. Furthermore, BC 005927 is frequently upregulated in GC samples and increased BC 005927 expression was correlated with a higher tumor‐node‐metastasis stage. GC patients with higher BC 005927 expression had poorer prognoses than those with lower expression. Additional experiments showed that BC 005927 expression is induced by hypoxia inducible factor‐1 alpha ( HIF ‐1α); Ch IP assay and luciferase reporter assays confirmed that this lnc RNA is a direct transcriptional target of HIF ‐1α. Next, we found that EPHB 4, a metastasis‐related gene, is regulated by BC 005927 and that the expression of EPHB 4 was positively correlated with that of BC 005927 in the clinical GC samples assessed. Intriguingly,  EPHB 4 expression was also increased under hypoxia, and its upregulation by BC 005927 resulted in hypoxia‐induced GC cell metastasis. These results advance the current understanding of the role of BC 005927 in the regulation of hypoxia signaling and offer new avenues for the development of therapeutic interventions against cancer progression.
ISSN:1347-9032
1349-7006
DOI:10.1111/cas.13519