A novel long non-coding RNA ENST00000480739 suppresses tumour cell invasion by regulating OS-9 and HIF-1α in pancreatic ductal adenocarcinoma

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 inter...

Descripción completa

Detalles Bibliográficos
Autores principales: Sun, Y-W, Chen, Y-F, Li, J, Huo, Y-M, Liu, D-J, Hua, R, Zhang, J-F, Liu, W, Yang, J-Y, Fu, X-L, Yan, T, Hong, J, Cao, H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Molecular Diagnostics
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260035/
https://www.ncbi.nlm.nih.gov/pubmed/25314054
http://dx.doi.org/10.1038/bjc.2014.520
_version_ 1782348111318876160
author Sun, Y-W
Chen, Y-F
Li, J
Huo, Y-M
Liu, D-J
Hua, R
Zhang, J-F
Liu, W
Yang, J-Y
Fu, X-L
Yan, T
Hong, J
Cao, H
author_facet Sun, Y-W
Chen, Y-F
Li, J
Huo, Y-M
Liu, D-J
Hua, R
Zhang, J-F
Liu, W
Yang, J-Y
Fu, X-L
Yan, T
Hong, J
Cao, H
author_sort Sun, Y-W
collection PubMed
description 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-1α (HIF-1α) 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-1α. 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.
format Online
Article
Text
id pubmed-4260035
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-42600352015-11-25 A novel long non-coding RNA ENST00000480739 suppresses tumour cell invasion by regulating OS-9 and HIF-1α in pancreatic ductal adenocarcinoma Sun, Y-W Chen, Y-F Li, J Huo, Y-M Liu, D-J Hua, R Zhang, J-F Liu, W Yang, J-Y Fu, X-L Yan, T Hong, J Cao, H Br J Cancer Molecular Diagnostics 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-1α (HIF-1α) 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-1α. 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. Nature Publishing Group 2014-11-25 2014-10-14 /pmc/articles/PMC4260035/ /pubmed/25314054 http://dx.doi.org/10.1038/bjc.2014.520 Text en Copyright © 2014 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/3.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Molecular Diagnostics
Sun, Y-W
Chen, Y-F
Li, J
Huo, Y-M
Liu, D-J
Hua, R
Zhang, J-F
Liu, W
Yang, J-Y
Fu, X-L
Yan, T
Hong, J
Cao, H
A novel long non-coding RNA ENST00000480739 suppresses tumour cell invasion by regulating OS-9 and HIF-1α in pancreatic ductal adenocarcinoma
title A novel long non-coding RNA ENST00000480739 suppresses tumour cell invasion by regulating OS-9 and HIF-1α in pancreatic ductal adenocarcinoma
title_full A novel long non-coding RNA ENST00000480739 suppresses tumour cell invasion by regulating OS-9 and HIF-1α in pancreatic ductal adenocarcinoma
title_fullStr A novel long non-coding RNA ENST00000480739 suppresses tumour cell invasion by regulating OS-9 and HIF-1α in pancreatic ductal adenocarcinoma
title_full_unstemmed A novel long non-coding RNA ENST00000480739 suppresses tumour cell invasion by regulating OS-9 and HIF-1α in pancreatic ductal adenocarcinoma
title_short A novel long non-coding RNA ENST00000480739 suppresses tumour cell invasion by regulating OS-9 and HIF-1α in pancreatic ductal adenocarcinoma
title_sort novel long non-coding rna enst00000480739 suppresses tumour cell invasion by regulating os-9 and hif-1α in pancreatic ductal adenocarcinoma
topic Molecular Diagnostics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260035/
https://www.ncbi.nlm.nih.gov/pubmed/25314054
http://dx.doi.org/10.1038/bjc.2014.520
work_keys_str_mv AT sunyw anovellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT chenyf anovellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT lij anovellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT huoym anovellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT liudj anovellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT huar anovellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT zhangjf anovellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT liuw anovellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT yangjy anovellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT fuxl anovellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT yant anovellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT hongj anovellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT caoh anovellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT sunyw novellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT chenyf novellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT lij novellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT huoym novellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT liudj novellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT huar novellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT zhangjf novellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT liuw novellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT yangjy novellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT fuxl novellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT yant novellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT hongj novellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma
AT caoh novellongnoncodingrnaenst00000480739suppressestumourcellinvasionbyregulatingos9andhif1ainpancreaticductaladenocarcinoma

Ejemplares similares