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Altered expression of hypoxia-inducible factor-1? (HIF-1?) and its regulatory genes in gastric cancer tissues.

ABSTRACT: Tissue hypoxia induces reprogramming of cell metabolism and may result in normal cell transformation and cancer progression. Hypoxia-inducible factor 1-alpha (HIF-1?), the key transcription factor, plays an important role in gastric cancer development and progression. This study aimed to investigate the underlying regulatory signaling pathway in gastric cancer using gastric cancer tissue specimens. The integration of gene expression profile and transcriptional regulatory element database (TRED) was pursued to identify HIF-1? ? NF?B1 ? BRCA1 ? STAT3 ? STAT1 gene pathways and their regulated genes. The data showed that there were 82 differentially expressed genes that could be regulated by these five transcription factors in gastric cancer tissues and these genes formed 95 regulation modes, among which seven genes (MMP1, TIMP1, TLR2, FCGR3A, IRF1, FAS, and TFF3) were hub molecules that are regulated at least by two of these five transcription factors simultaneously and were associated with hypoxia, inflammation, and immune disorder. Real-Time PCR and western blot showed increasing of HIF-1? in mRNA and protein levels as well as TIMP1, TFF3 in mRNA levels in gastric cancer tissues. The data are the first study to demonstrate HIF-1?-regulated transcription factors and their corresponding network genes in gastric cancer. Further study with a larger sample size and more functional experiments is needed to confirm these data and then translate into clinical biomarker discovery and treatment strategy for gastric cancer.

SUBMITTER: Wang J

PROVIDER: S-EPMC4057318 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Altered expression of hypoxia-inducible factor-1α (HIF-1α) and its regulatory genes in gastric cancer tissues.

Wang Jihan J Ni Zhaohui Z Duan Zipeng Z Wang Guoqing G Li Fan F

PloS one 20140613 6

Tissue hypoxia induces reprogramming of cell metabolism and may result in normal cell transformation and cancer progression. Hypoxia-inducible factor 1-alpha (HIF-1α), the key transcription factor, plays an important role in gastric cancer development and progression. This study aimed to investigate the underlying regulatory signaling pathway in gastric cancer using gastric cancer tissue specimens. The integration of gene expression profile and transcriptional regulatory element database (TRED) ...[more]

PMID: 24927122

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Project description:IntroductionSystemic sclerosis is an autoimmune disease characterized by tissue fibrosis and microangiopathy. Vascular changes such as a decrease in capillary density diminish blood flow and impair tissue oxygenation. Reliable ways to monitor disease activity and predict disease progression are desired in the process of patient selection for clinical trials and to optimize individual patient outcomes. Hypoxia-inducible factor-1 (HIF-1) is a dimeric protein complex that plays an integral role in the body's response to hypoxia. Our study aimed to investigate the potential abnormalities of HIF-1α plasma concentration and its possible association with disease activity and vascular abnormalities in patients with systemic sclerosis.MethodsBlood plasma levels of HIF-1α were measured in patients with systemic sclerosis (n = 50) and in healthy individuals (n = 30) using commercially available ELISA test kits.ResultsThe results showed a marked increase in HIF-1α levels in patients with systemic sclerosis (3.042 ng/ml [2.295-7.749]) compared to the control group (1.969 ng/ml [1.531-2.903] p < 0.01). Patients with diffuse cutaneous SSc (2.803 ng/ml, IQR 2.221-8.799) and limited cutaneous SSc (3.231 ng/ml, IQR 2.566-5.502) exhibited elevated serum HIF-1α levels compared to the control group (p < 0.01). We found a notable increase in HIF-1α plasma concentration in patients with an "active" pattern (6.625 ng/ml, IQR 2.488-11.480) compared to those with either an "early" pattern (2.739, IQR 2.165-3.282, p < 0.05) or a "late" pattern (2.983 ng/ml, IQR 2.229-3.386, p < 0.05). Patients with no history of digital ulcers had significantly higher levels of HIF-1α (4.367 ng/ml, IQR 2.488-9.462) compared to patients with either active digital ulcers (2.832 ng/ml, IQR 2.630-3.094, p < 0.05) or healed digital ulcers (2.668 ng/ml, IQR 2.074-2.983, p < 0.05).ConclusionsOur results indicate that HIF-1α may serve as a biomarker in assessing microcirculatory changes in individuals with systemic sclerosis.

Dataset Information

Altered expression of hypoxia-inducible factor-1? (HIF-1?) and its regulatory genes in gastric cancer tissues.

Publications

Altered expression of hypoxia-inducible factor-1α (HIF-1α) and its regulatory genes in gastric cancer tissues.

Similar Datasets

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