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2017 ; 9
(10
): 4440-4449
Nephropedia Template TP
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English Wikipedia
RNAi-mediated silencing of NOX4 inhibited the invasion of gastric cancer cells
through JAK2/STAT3 signaling
#MMPMID29118906
Gao X
; Sun J
; Huang C
; Hu X
; Jiang N
; Lu C
Am J Transl Res
2017[]; 9
(10
): 4440-4449
PMID29118906
show ga
NADPH oxidase 4 (NOX4) is a member of the NADPH oxidase (NOX) family of enzymes
and has been found abnormally expressed in human cancers. However, its role in
gastric cancer (GC) is still unclear. In the current study, we reported that NOX4
expression levels were significantly up-regulated in GC tissues compared to
normal tissues (P<0.0001). Higher NOX4 expression was significantly associated
with poorer overall survival in GC patients. Silencing NOX4 in two NOX4 high
expression GC cell lines, MGC-803 and BGC-823 cells, did not affect cell
proliferation, while inhibited cell adhesion and cell invasion of GC cells.
Furthermore, Gene set enrichment analysis (GSEA) results indicated that NOX4
expression was strongly associated with cell migration, epithelial-mesenchymal
transition (EMT) and Janus kinase/signal transducer and activator of
transcription (JAK/STAT) signaling pathways. More interestingly, Interleukin-6
(IL-6) increased the invasion ability and activation of JAK2/STAT3 of MGC-803 and
BGC-823 cells. Such effects were attenuated by NOX4 silencing. Overexpression of
NOX4 in one NOX4 low expression GC cell line, SGC-7901 cells, significantly
promoted cell invasion, which was impaired by treatment of JAK2 inhibitor, AG490.
AG490 inhibited STAT3 activation in SW1990 cells. NOX4 may exert its function
through JAK2/STAT3 pathway. In summary, the findings of this study indicate that
NOX4 may promote the development of GC, potentially representing a novel
prognostic marker for overall survival in GC.