Transcriptional regulatory networks in human lung adenocarcinoma

Abstract

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 proteinβ (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 receptorII (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.