7P The regulation of FOXP3 expression by GLI-1 in non-small cell lung cancer cells and its influence on lung cancer cell stemness

Background: Later numerous publications have demonstrated that lymphocytic FOXP3 is significantly associated with immune suppression. However, there are conflict data concerning its function among malignant cells. In colorectal cancer cells the inhibition of FOXP3 expression can result in increased cancer stemness. However whether this is the case in lung CSC or whether it is related to GLI-1 remains unclear. Methods: In this study, a series of in vivo and in vitro experiments will be conducted to clarify the regulation of FOXP3 expression in non-small-cell lung cancer cells, and its influence upon lung cancer cell stemness. Results: The cells with FOXP3 over expression and negative controls were applied for mRNA expression microarray experiments, and the results showed that when the expression of FOXP3 was up regulated, the expression of GLI-1 was oppositely regulated. Three NSCLC cell lines were treated with NNK for different periods. The results show that with the treat time progressing, the expression of FOXP3 was up regulated with the expression of GLI-1 down regulated. When the FOXP3 expression was up regulated, the expression of GLI-1 was suppressed, while the expression of cancer stem cell markers includes SOX2, Nanog and CD133 were also up regulated, which meant the cancer stemness increased. When the GLI-1 expression was up regulated, the expression of FOXP3 was increased, and the expression of cancer stem cell markers include SOX2 and Nanog were also up regulated, which meant the cancer stemness increased. For tumors with FOXP3 over expressed, the expression of GLI-1 was up regulated and the cancer stemness increased. GLI-1 and FOXP3 might bind with each other inside cells. It was easier for H460-FOXP3 cells to form tumor sphere, and the diameter is much larger. Conclusions: GLI-1 might influence lung cancer stem cells by regulating the expression of FOXP3. Legal entity responsible for the study: Chinese University of Hong Kong Funding: General Research Fund from Chinese University of Hong Kong Disclosure: All authors have declared no conflicts of interest.