Gene Regulation Network Based Analysis Associated with TGF-βeta Stimulation in Lung Adenocarcinoma Cells

Transforming growth factor (TGF)-β is over-expressed in a wide variety of cancers such as lung adenocarcinoma. TGF-β plays a major role in cancer progression through regulating cancer cell proliferation and remodeling of the tumor micro-environment. However, it is still a great challenge to explain the phenotypic effects caused by TGF-β stimulation and the effect of TGF-β stimulation on tumor micro-environment.

To address this issue, in the present study we used two time-course microarray data in human lung adenocarcinoma cells and applied bioinformatics methods to explore the gene regulation network responding to TGF-β stimulation in lung adenocarcinoma cells.

The time-dependent reverse-engineering method, protein-protein interaction network analyses, and calculation of the similarity measures between the links were used to construct gene regulatory network and to extract gene clusters.

Utilizing the constructed gene regulation network, we predicted NEFL and LUC7A show the opposite and the same change with C21orf90 if HAND2 is knocked-out after treatment with TGF-β₁ for 4 hours and for 12 hours respectively. FGG and HSPC009 are predicted to display the opposite change with NEFL if CSMD1 is knocked out after treatment with TGF-β₁ for 12 hours. Additionally, by integrating two datasets, we specially identified several nested clusters which included those genes regulated by TGF-β stimulation in lung adenocarcinoma cells.

Our analysis can help a better understanding regarding how TGF-β stimulation causes the expression change of a number of the genes and provide a novel insight into TGF-β stimulation effect on lung adenocarcinoma cells.