Cargando…
CypA, a Gene Downstream of HIF-1α, Promotes the Development of PDAC
Hypoxia-inducible factor-1α (HIF-1α) is a highly important transcription factor involved in cell metabolism. HIF-1α promotes glycolysis and inhibits of mitochondrial respiration in pancreatic ductal adenocarcinoma (PDAC). In response to tumor hypoxia, cyclophilin A (CypA) is over-expressed in variou...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963943/ https://www.ncbi.nlm.nih.gov/pubmed/24662981 http://dx.doi.org/10.1371/journal.pone.0092824 |
_version_ | 1782308568368676864 |
---|---|
author | Zhang, Huan Chen, Jing Liu, Fenghua Gao, Chuntao Wang, Xiuchao Zhao, Tiansuo Liu, Jingcheng Gao, Song Zhao, Xiao Ren, He Hao, Jihui |
author_facet | Zhang, Huan Chen, Jing Liu, Fenghua Gao, Chuntao Wang, Xiuchao Zhao, Tiansuo Liu, Jingcheng Gao, Song Zhao, Xiao Ren, He Hao, Jihui |
author_sort | Zhang, Huan |
collection | PubMed |
description | Hypoxia-inducible factor-1α (HIF-1α) is a highly important transcription factor involved in cell metabolism. HIF-1α promotes glycolysis and inhibits of mitochondrial respiration in pancreatic ductal adenocarcinoma (PDAC). In response to tumor hypoxia, cyclophilin A (CypA) is over-expressed in various cancer types, and is associated with cell apoptosis, tumor invasion, metastasis, and chemoresistance in PDAC. In this study, we showed that both HIF-1α and CypA expression were significantly associated with lymph node metastasis and tumor stage. The expression of CypA was correlated with HIF-1α. Moreover, the mRNA and protein expression of CypA markedly decreased or increased following the suppression or over-expression of HIF-1α in vitro. Chromatin immunoprecipitation analysis showed that HIF-1α could directly bind to the hypoxia response element (HRE) in the CypA promoter regions and regulated CypA expression. Consistent with other studies, HIF-1α and CypA promoted PDAC cell proliferation and invasion, and suppressed apoptosis in vitro. Furthermore, we proved the combination effect of 2-methoxyestradiol and cyclosporin A both in vitro and in vivo. These results suggested that,CypA, a gene downstream of HIF-1α, could promote the development of PDAC. Thus, CypA might serve as a potential therapeutic target for PDAC. |
format | Online Article Text |
id | pubmed-3963943 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39639432014-03-27 CypA, a Gene Downstream of HIF-1α, Promotes the Development of PDAC Zhang, Huan Chen, Jing Liu, Fenghua Gao, Chuntao Wang, Xiuchao Zhao, Tiansuo Liu, Jingcheng Gao, Song Zhao, Xiao Ren, He Hao, Jihui PLoS One Research Article Hypoxia-inducible factor-1α (HIF-1α) is a highly important transcription factor involved in cell metabolism. HIF-1α promotes glycolysis and inhibits of mitochondrial respiration in pancreatic ductal adenocarcinoma (PDAC). In response to tumor hypoxia, cyclophilin A (CypA) is over-expressed in various cancer types, and is associated with cell apoptosis, tumor invasion, metastasis, and chemoresistance in PDAC. In this study, we showed that both HIF-1α and CypA expression were significantly associated with lymph node metastasis and tumor stage. The expression of CypA was correlated with HIF-1α. Moreover, the mRNA and protein expression of CypA markedly decreased or increased following the suppression or over-expression of HIF-1α in vitro. Chromatin immunoprecipitation analysis showed that HIF-1α could directly bind to the hypoxia response element (HRE) in the CypA promoter regions and regulated CypA expression. Consistent with other studies, HIF-1α and CypA promoted PDAC cell proliferation and invasion, and suppressed apoptosis in vitro. Furthermore, we proved the combination effect of 2-methoxyestradiol and cyclosporin A both in vitro and in vivo. These results suggested that,CypA, a gene downstream of HIF-1α, could promote the development of PDAC. Thus, CypA might serve as a potential therapeutic target for PDAC. Public Library of Science 2014-03-24 /pmc/articles/PMC3963943/ /pubmed/24662981 http://dx.doi.org/10.1371/journal.pone.0092824 Text en © 2014 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Zhang, Huan Chen, Jing Liu, Fenghua Gao, Chuntao Wang, Xiuchao Zhao, Tiansuo Liu, Jingcheng Gao, Song Zhao, Xiao Ren, He Hao, Jihui CypA, a Gene Downstream of HIF-1α, Promotes the Development of PDAC |
title | CypA, a Gene Downstream of HIF-1α, Promotes the Development of PDAC |
title_full | CypA, a Gene Downstream of HIF-1α, Promotes the Development of PDAC |
title_fullStr | CypA, a Gene Downstream of HIF-1α, Promotes the Development of PDAC |
title_full_unstemmed | CypA, a Gene Downstream of HIF-1α, Promotes the Development of PDAC |
title_short | CypA, a Gene Downstream of HIF-1α, Promotes the Development of PDAC |
title_sort | cypa, a gene downstream of hif-1α, promotes the development of pdac |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963943/ https://www.ncbi.nlm.nih.gov/pubmed/24662981 http://dx.doi.org/10.1371/journal.pone.0092824 |
work_keys_str_mv | AT zhanghuan cypaagenedownstreamofhif1apromotesthedevelopmentofpdac AT chenjing cypaagenedownstreamofhif1apromotesthedevelopmentofpdac AT liufenghua cypaagenedownstreamofhif1apromotesthedevelopmentofpdac AT gaochuntao cypaagenedownstreamofhif1apromotesthedevelopmentofpdac AT wangxiuchao cypaagenedownstreamofhif1apromotesthedevelopmentofpdac AT zhaotiansuo cypaagenedownstreamofhif1apromotesthedevelopmentofpdac AT liujingcheng cypaagenedownstreamofhif1apromotesthedevelopmentofpdac AT gaosong cypaagenedownstreamofhif1apromotesthedevelopmentofpdac AT zhaoxiao cypaagenedownstreamofhif1apromotesthedevelopmentofpdac AT renhe cypaagenedownstreamofhif1apromotesthedevelopmentofpdac AT haojihui cypaagenedownstreamofhif1apromotesthedevelopmentofpdac |