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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Exp+Clin+Cancer+Res
2017 ; 36
(1
): 54
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Long non-coding RNA NKILA inhibits migration and invasion of non-small cell lung
cancer via NF-?B/Snail pathway
#MMPMID28412955
Lu Z
; Li Y
; Wang J
; Che Y
; Sun S
; Huang J
; Chen Z
; He J
J Exp Clin Cancer Res
2017[Apr]; 36
(1
): 54
PMID28412955
show ga
BACKGROUND: Numerous studies have shown that long non-coding RNAs (lncRNAs) play
key roles during multiple cancer processes, such as cell proliferation,
apoptosis, migration and invasion. The previous studies found that NKILA
interacted with and suppressed the nuclear translocation of NF-KappaB, which
influenced metastasis and prognosis in breast cancer. However the clinical
significance and biological role of NKILA in non-small cell lung cancer (NSCLC)
remains unknown. METHODS: We examined expression levels of NKILA in 106 pairs of
NSCLC tissues and cell lines. The expression level of NKILA after TGF-?1
stimulation also was examined by qRT-PCR and validated by Chromatin
immunoprecipitation (ChIP). Gain-of-function and loss-of-function assays were
performed to examine the effect of NKILA on proliferation, migration and invasion
of NSCLC cells. RNA immunoprecipitation (RIP), western blot and rescue
experiments were carried out to reveal the interrelation between NKILA, NF-?B and
EMT signal pathway. RESULTS: The expression of NKILA was down-regulated in NSCLC
cancer tissues compared with matched adjacent noncancerous tissues, and lower
NKILA expression in tumor tissues were significantly correlated with lymph node
metastasis and advanced TNM stage. We found that the expression of NKILA was
mainly regulated by classical TGF-? signal pathway in NSCLC cells rather than
NF-?B pathway reported in breast cancer. Gain and loss of function assays found
that NKILA inhibited migration, invasion and viability of NSCLC cells.
Mechanistic study showed that NKILA attenuated Snail expression via inhibiting
the phosphorylation of I?B? and NF-?B activation, subsequently suppressed the
expression of markers of epithelial-mesenchymal transition process. CONCLUSIONS:
The present study found that the expression of NKILA was downregulated in tumor
tissues of NSCLC, which improved the metastasis of NSCLC patients. In vitro
studies further clarified that the expression of NKILA was regulated through
classical TGF-? signal pathway, which subsequently inhibited migration and
invasion of NSCLC cells through interfering NF-?B/Snail signal pathway in NSCLC
cells.