Identification of key pathways and genes in lung carcinogenesis

Jin,Xiang; Liu,Xingang; Zhang,Zhen; Guan,Yinghui; Xv,Ren; Li,Jun

doi:10.3892/ol.2018.9203

Identification of key pathways and genes in lung carcinogenesis

Authors:
- Xiang Jin
- Xingang Liu
- Zhen Zhang
- Yinghui Guan
- Ren Xv
- Jun Li
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Affiliations: Department of Respiration, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of ICU, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of PICU, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Pneumology, Jinan Central Hospital, Jinan, Shandong 250013, P.R. China
Published online on: July 24, 2018 https://doi.org/10.3892/ol.2018.9203
Pages: 4185-4192
Copyright: © Jin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to identify key pathways and genes in the pathogenesis of lung cancer. The GSE10072 dataset was downloaded from the Gene Expression Omnibus database. Protein‑protein interaction data were collected from Human Protein Reference Database, and 201 pathways were downloaded from the Kyoto Encyclopedia of Genes and Genomes database. Signaling network impact analysis was performed to identify enriched pathways, followed by the construction of a pathway‑pathway crosstalk network. Benzopyrene was used to treat normal human lung cells at concentrations of 0.01, 0.1, 1 and 10 µM, and cell viability was measured. Furthermore, growth arrest and DNA damage inducible β (GADD45B), p53, cyclin B, Akt and nuclear factor (NF)‑κB protein levels were also measured via western blotting. Impact analysis identified 11 enriched lung cancer‑associated KEGG pathways, including ‘complement and coagulation cascades’, ‘ECM‑receptor interaction’, ‘P53 signaling pathway’, ‘cell adhesion molecules’ and ‘focal adhesion’. In addition, cell cycle, ‘drug metabolism‑cytochrome P450’, ‘metabolic pathways’, ‘pathways in cancer’, ‘focal adhesion’ and ‘antigen processing and presentation’ were central in the pathway‑pathway cross‑talk network. Furthermore, the upregulated gene GADD45B was associated with three of the pathways, including an activated pathway (‘MAPK signaling pathway’) and two repressed pathways (‘cell cycle’ and ‘P53 pathway’). Western blotting demonstrated that the expression of NF‑κB, Akt and GADD45B increased over time in lung cells treated with benzopyrene, whereas the expression levels of cyclin B and P53 decreased. In conclusion, GADD45B may contribute to lung carcinogenesis via affecting the MAPK, P53 signaling and cell cycle pathways.

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