Brain-derived neurotrophic factor serves as a tumor-trophic factor for lung cancer by controlling cell cycle

Abstract

Abstract Background The nervous system plays a key role in the lung development, and its dysfunction might be related to the occurrence of lung cancer. In fact, neurotrophic factors, especially brain-derived neurotrophic factor (BDNF), promote tumor malignancy, in which, however, the mechanism remains to be illustrated. Methods Lung cancer cell-A549 cell line was included in the study. HSV-BDNF-ORF/HSV-BDNF-shRNA vectors were prepared and transfected into A549 cells. The proliferation and migration were detected by xCELLigence Real-Time Cell Analyzer. Cell apoptosis was determined through Flow cytometry. The gene expression on transcriptome level was detected by gene microarray analysis. Bioinformatics analysis consisted of GO, KEGG and String analysis. Results Firstly, we found that the expression of BDNF in A549 cells was increased. Then we successfully constructed HSV-BDNF-ORF and HSV-BDNF-shRNA vectors, which could lead to the increase or decrease in BDNF expression after transfected into A549 cells, respectively. Moreover, BDNF served as “tumor-trophic factor” that promoted A549 cells proliferation and migration, while BDNF knockdown triggered the cell apoptosis of A549 cells. Mechanistically, BDNF-induced cell proliferation might be linked with the upregulation of cell cycle-related genes. The cell apoptosis triggered by BDNF knockdown should be attributing to the up-regulated apoptosis-associated genes. Conclusion BDNF served as a tumor-trophic factor mediating lung cancer cell proliferation and apoptosis by regulating the cell cycle-related and cell apoptosis associated-genes, indicating that BDNF might exert significant impact on treating lung cancer.