CypA, a Gene Downstream of HIF-1α, Promotes the Development of PDAC

Zhang, Huan; Chen, Jing; Li, Fenghua; Gao, Chuntao; Wang, Xiuchao; Zhao, Tiansuo; Liu, Jingcheng; Gao, Song; Zhao, Xiao Ling; Ren, He; Hao, Jihui

doi:10.1371/journal.pone.0092824

Cited by 34 publications

(39 citation statements)

References 39 publications

(57 reference statements)

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“…Therefore, the study of hypoxic microenvironments may have a crucial function in targeted therapy adopted by clinics in the future. Hypoxia-inducible factor-1α (HIF-1α) is an essential transcriptional regulatory factor in hypoxia microenvironments and has 100 types of downstream gene, including cell proliferation, angiogenesis and energy metabolism (8,9). A previous study indicated that the expression of HIF-1α, C-X-C motif chemokine receptor 4 (CXCR4) and vascular endothelial growth factor (VEGF) is involved in tumor progression, angiogenesis, metastasis and survival, and their expression may be induced by hypoxia (10).…”

Section: Introductionmentioning

confidence: 99%

CoCl2 increases the expression of hypoxic markers HIF‑1α, VEGF and CXCR4 in breast cancer MCF‑7 cells

Zhang

2017

Oncol Lett

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Abstract. The aim of the present study was to investigate the effect of a hypoxic environment on the biological behavior of breast cancer MCF-7 cells, using CoCl 2 to mimic the hypoxia model in breast cancer cells. Using 50, 100, 150 and 200 µM CoCl 2 as a hypoxic inducer, a hypoxic model was established in MCF-7 cells in vitro. MTT, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and western blotting assays were performed to detect MCF-7 cell proliferation under hypoxic conditions and the expression of the hypoxic markers hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and C-X-C motif chemokine receptor 4 (CXCR4) mRNA and that of the associated proteins. The RT-qPCR results revealed that there were no obvious changes in the expression of HIF-1α mRNA; however, the expression of CXCR4 and VEGF mRNA increased significantly following treatment with different CoCl 2 concentrations (P<0.05). The results of western blotting identified that CoCl 2 significantly induced the expression of HIF-1α, CXCR4 and VEGF proteins (P<0.05). The MTT assay revealed that different concentrations of CoCl 2 inhibited the proliferation of MCF-7 cells. The TUNEL assay demonstrated that CoCl 2 was able to trigger apoptosis of MCF-7 cells. Therefore, the results of the present study identified that CoCl 2 is able to control MCF-7 cell proliferation and apoptosis, also increasing the expression of HIF-1α, CXCR4 and VEGF. The present study may aid the discovery of a novel method to prevent cell damage and decrease cell proliferation in order to prevent the occurrence and development of breast cancer.

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Section: Introductionmentioning

confidence: 99%

CoCl2 increases the expression of hypoxic markers HIF‑1α, VEGF and CXCR4 in breast cancer MCF‑7 cells

Zhang

2017

Oncol Lett

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“…Cyclophilin A (CyPA) was originally discovered as a cellular factor with high affinity for the immunosuppressant cyclosporine A (CsA) [6]. Previous studies have demonstrated that ischemia/reperfusion (I/R) and hypoxia can induce expression of CyPA [7][8][9]. CyPA can be also secreted from monocytes/macrophages [10], endothelial cells [11], and vascular smooth muscle cells [12] in response to ROS.…”

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confidence: 99%

Inhibition of cyclophilin A suppresses H₂O₂‐enhanced replication of HCMV through the p38 MAPK signaling pathway

Xiao¹,

Song²,

Deng³

et al. 2016

FEBS Open Bio

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Human cytomegalovirus (HCMV) infection can be accelerated by intracellular and extracellular hydrogen peroxide (H2O2) stimulation, mediated by the activation of the p38 mitogen‐activated protein kinase (MAPK) pathway. However, it remains unknown whether host gene expression is involved in H2O2‐upregulated HCMV replication. Here, we show that the expression of the host gene, cyclophilin A (CyPA), could be facilitated by treatment with H2O2 in a dose‐dependent manner. Experiments with CyPA‐specific siRNA, or with cyclosporine A, an inhibitor of CyPA, confirmed that H2O2‐mediated upregulation of HCMV replication is specifically mediated by upregulation of CyPA expression. Furthermore, depletion or inhibition of CyPA reduced H2O2‐induced p38 activation, consistent with that of H2O2‐upregulated HCMV lytic replication. These results show that H2O2 is capable of activating ROS‐CyPA–p38 MAPK interactions to enhance HCMV replication.

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“…Consistent with that, loss of CypA expression increased mitochondrial membrane depolarization and reduced survival following H 2 O 2 treatment [34]. Furthermore, there is evidence that CypA is transcriptionally regulated by the hypoxia inducible factor (HIF)-1α under hypoxic conditions [34] [61] and it is suggested that up-regulated CypA desensitises cells to hypoxia-induced cell death [34].…”

Section: Cyclophilins and Chemoresistancementioning

confidence: 59%

Cyclophilin function in Cancer; lessons from virus replication

Lavin¹

2015

CMP

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Cyclophilins belong to a group of proteins that possess peptidyl prolyl isomerase activity and catalyse the cis-trans conversion of proline peptide bonds. Cyclophilin members play important roles in protein folding and as molecular chaperones, in addition to a wellestablished role as host factors required for completion of the virus life cycle. Members of the cyclophilin family are overexpressed in a range of human malignancies including hepatocellular cancer, pancreatic cancer, non-small cell lung cancer, gastric cancer, colorectal cancer and glioblastoma multiforme, however, their precise role in tumourigenesis remains unclear. In recent years, mounting evidence supports a role for prolyl isomerisation during mammalian cell division; a process with striking similarity to plasma membrane remodelling during virus replication. Here we will summarise our current understanding of the role of cyclophilins in cancer. We will review the function of cyclophilins during mammalian cell division and during HIV-1 infection, and highlight common processes involving members of the ESCRT and Rab GTPase families. IntroductionThe interconversion of protein backbone between cis and trans, catalysed by peptidyl prolyl isomerases (PPIases), is an important event that alters protein structure and activity and regulates a wide spectrum of cellular functions in normal physiological processes. For example, isomerisation mediates the spatiotemporal control of fundamental processes including cell cycle progression, cell proliferation and cell death [1][2][3][4]. In recent years, mounting evidence implicates deregulated isomerase activity in a range of age-related pathologies including neurodegeneration, cardiovascular disease and cancer [5]. As a result, isomerases have gained significant interest as therapeutic targets in the treatment of these diseases.

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CypA, a Gene Downstream of HIF-1α, Promotes the Development of PDAC

Cited by 34 publications

References 39 publications

CoCl2 increases the expression of hypoxic markers HIF‑1α, VEGF and CXCR4 in breast cancer MCF‑7 cells

CoCl2 increases the expression of hypoxic markers HIF‑1α, VEGF and CXCR4 in breast cancer MCF‑7 cells

Inhibition of cyclophilin A suppresses H₂O₂‐enhanced replication of HCMV through the p38 MAPK signaling pathway

Cyclophilin function in Cancer; lessons from virus replication

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CypA, a Gene Downstream of HIF-1α, Promotes the Development of PDAC

Cited by 34 publications

References 39 publications

CoCl2 increases the expression of hypoxic markers HIF‑1α, VEGF and CXCR4 in breast cancer MCF‑7 cells

CoCl2 increases the expression of hypoxic markers HIF‑1α, VEGF and CXCR4 in breast cancer MCF‑7 cells

Inhibition of cyclophilin A suppresses H2O2‐enhanced replication of HCMV through the p38 MAPK signaling pathway

Cyclophilin function in Cancer; lessons from virus replication

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Inhibition of cyclophilin A suppresses H₂O₂‐enhanced replication of HCMV through the p38 MAPK signaling pathway