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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
2015 ; 34
(ä): 116
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Long noncoding RNA lncTCF7, induced by IL-6/STAT3 transactivation, promotes
hepatocellular carcinoma aggressiveness through epithelial-mesenchymal
transition
#MMPMID26452542
Wu J
; Zhang J
; Shen B
; Yin K
; Xu J
; Gao W
; Zhang L
J Exp Clin Cancer Res
2015[Oct]; 34
(ä): 116
PMID26452542
show ga
BACKGROUND: Accumulating evidence suggests the pro-inflammatory cytokine
interleukin-6 (IL-6) in tumor microenvironment may promote the development of
hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely
unknown. METHODS: The expression and promoter activity of lncTCF7 were measured
by quantitative real-time polymerase chain reaction (qRT-PCR) and luciferase
reporter assay. The function of the STAT3 binding site in the lncTCF7 promoter
region was tested by luciferase reporter assay with nucleotide substitutions. The
binding of STAT3 to the lncTCF7 promoter was confirmed by chromatin
immunoprecipitation assay (CHIP) in vivo. The effects of decreasing STAT3 with
small interference RNA and inhibiting STAT3 activation by small molecular
inhibitor on lncTCF7 expression were also determined. RESULTS: We demonstrate
that IL-6 could induce lncTCF7 expression in a time- and dose-dependent manner,
and we showed that IL-6 transcriptionally activated the expression of lncTCF7 in
HCC cells by activating STAT3, a transcription activator which binds to promoter
regions of lncTCF7. Furthermore, knocking-down STAT3 and inhibiting STAT3
activation reduced lncTCF7 expression. Importantly, RNA interference-based
attenuation of lncTCF7 prevented IL-6-induced EMT and cell invasion. CONCLUSION:
Thus, these data provides evidence to the existence of an aberrant IL-6/STAT3/
lncTCF7 signaling axis that leads to HCC aggressiveness through EMT induction,
which could be novel therapeutic targets in malignancies.