title: Altered expression of hypoxia-inducible factor-1α (HIF-1α) 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-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) was pursued to identify HIF-1α ↔ NFκB1 → 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-1α 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-1α-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.
authors.affiliation: Department of Pathogenobiology, Jilin Key Laboratory of Biomedical Materials, College of Basic Medical Science, Jilin University, Changchun, China.
authors.forename: Jihan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathogenobiology, Jilin Key Laboratory of Biomedical Materials, College of Basic Medical Science, Jilin University, Changchun, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Ni
authors.affiliation: Department of Pathogenobiology, Jilin Key Laboratory of Biomedical Materials, College of Basic Medical Science, Jilin University, Changchun, China.
authors.forename: Zipeng
authors.initials: Z
authors.lastname: Duan
authors.affiliation: Department of Pathogenobiology, Jilin Key Laboratory of Biomedical Materials, College of Basic Medical Science, Jilin University, Changchun, China; The Key Laboratory for Bionics Engineering, Ministry of Education, China, Jilin University, Changchun, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Pathogenobiology, Jilin Key Laboratory of Biomedical Materials, College of Basic Medical Science, Jilin University, Changchun, China; The Key Laboratory for Bionics Engineering, Ministry of Education, China, Jilin University, Changchun, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Li
mesh_terms: D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D005809:Genes, Regulator / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D000071165:Trefoil Factor-3
chemical_list: C496124:FCGR3A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D010455:Peptides; D017452:Receptors, IgG; C082495:TFF3 protein, human; C560822:TIMP1 protein, human; C495342:TLR2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D051195:Toll-Like Receptor 2; D000071165:Trefoil Factor-3; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1