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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 Br+J+Cancer
2014 ; 111
(11
): 2131-41
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A novel long non-coding RNA ENST00000480739 suppresses tumour cell invasion by
regulating OS-9 and HIF-1? in pancreatic ductal adenocarcinoma
#MMPMID25314054
Sun YW
; Chen YF
; Li J
; Huo YM
; Liu DJ
; Hua R
; Zhang JF
; Liu W
; Yang JY
; Fu XL
; Yan T
; Hong J
; Cao H
Br J Cancer
2014[Nov]; 111
(11
): 2131-41
PMID25314054
show ga
BACKGROUND: Invasion and metastasis are the distinct biologic characteristics of
cancer, resulting in an exceptionally low 5-year survival rate in pancreatic
ductal adenocarcinoma (PDAC). Understanding in detail the mechanisms underlying
PDAC metastasis is critical for prevention and effective interventions. Long
non-coding RNAs (lncRNAs) have been documented as having a critical role in
cancer development and progression. METHODS: We examined the expression levels of
lncRNA ENST00000480739 and osteosarcoma amplified-9 (OS-9) mRNA in a cohort of 35
PDAC patients. Cell proliferation, invasion and migration were examined with and
without ENST00000480739 overexpression in PDAC cells. RESULTS: We determined that
the ENST00000480739 expression level was remarkably decreased in tumorous tissues
compared with their corresponding non-tumorous tissues. The expression of
ENST00000480739 was negatively associated with tumour node metastasis stage and
lymph node metastasis. In addition, ENST0000048073 was an independent prognostic
factor of survival time in PDAC patients following surgery. Besides, enforced
expression of ENST00000480739 suppressed PDAC cells' invasion in vitro.
Overexpression of ENST00000480739 significantly increased both mRNA and protein
levels of OS-9, and the luciferase assays confirmed that ENST00000480739
positively regulates OS-9 by activating the transcription level of the OS-9
promoter. We further found that ENST00000480739 may target hypoxia-inducible
factor-1? (HIF-1?) expression by upregulating OS-9. CONCLUSIONS: These findings
suggest that the frequently downregulated ENST00000480739 in PDAC contributes to
tumour metastasis and progression by regulating HIF-1?. Long non-coding RNA
ENST00000480739 may provide not only a therapeutic potential to suppress
metastasis but it may also be a novel biomarker for risk prognostication and
personal therapy screening of PDAC patients.