Transcriptional regulatory networks in human lung adenocarcinoma.
Lung adenocarcinoma (AC) is the most common histological subtype of lung             cancer worldwide and its absolute incidence is increasing markedly. Transcriptional             regulation is one of the most fundamental processes in lung AC development. However,             high-throughput functional analyses of multiple transcription factors and their             target genes in lung AC are rare. Thus, the objective of our study was to interpret             the mechanisms of human AC through the regulatory network using the GSE2514 microarray             data. Our results identified the genes peroxisome proliferator activated receptor-γ             (PPARG), CCAAT/enhancer binding protein β (CEBPB), ets variant 4 (ETV4), Friend             leukemia virus integration 1 (FLI1), T-cell acute lymphocytic leukemia 1 (TAL1)             and nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NFKB1)             as hub nodes in the transcriptome network. Among these genes, it appears that:             PPARG promotes the PPAR signaling pathway via the upregulation of lipoprotein             lipase (LPL) expression, but suppresses the cell cycle pathway via downregulation             of growth arrest and DNA-damage-inducible, γ (GADD45G) expression; ETV4 stimulates             matrix metallopeptidase 9 (MMP9) expression to induce the bladder cancer pathway;             FLI upregulates transforming growth factor, β receptor II (TGFBR2) expression             to activate TGF-β signaling and upregulates cyclin D3 (CCND3) expression to promote             the cell cycle pathway; NFKB1 upregulates interleukin 1, β (IL-1B) expression             and initiates the prostate cancer pathway; CEBPB upregulates IL-6 expression and             promotes pathways in cancer; and TAL1 promotes kinase insert domain receptor (KDR)             expression to promote the TGF-β signaling pathway. This transcriptional regulation             analysis may provide an improved understanding of the molecular mechanisms and             potential therapeutic targets in the treatment of lung AC.
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China.
Xiangrui
X
Meng
Peng
P
Lu
Hua
H
Bai
Peng
P
Xiao
Qingxia
Q
Fan
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017500:Adenovirus E1A Proteins / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D056743:Cyclin D3 / Q000378:metabolism; D015536:Down-Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D047495:PPAR gamma / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051789:Proto-Oncogene Protein c-fli-1 / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D015854:Up-Regulation; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D000097642:GADD45 Proteins
D017500:Adenovirus E1A Proteins; D051792:Basic Helix-Loop-Helix Proteins; D022782:CCAAT-Enhancer-Binding Protein-beta; D056743:Cyclin D3; D053583:Interleukin-1beta; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D008071:Lipoprotein Lipase; D020780:Matrix Metalloproteinase 9; D052002:NF-kappa B p50 Subunit; D047495:PPAR gamma; D017346:Protein Serine-Threonine Kinases; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D040301:Vascular Endothelial Growth Factor Receptor-2; D000097642:GADD45 Proteins; C545012:CEBPB protein, human; C079853:ETV4 protein, human; C078433:FLI1 protein, human; C489548:NFKB1 protein, human; C067143:TAL1 protein, human