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...
Gespeichert in:
Veröffentlicht in: | Cancer science 2018-04, Vol.109 (4), p.988-1000 |
---|---|
Hauptverfasser: | , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
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 |