FOXP3 Affects Migration Of Glioma Cells Through Regulating ARHGAP15 Expression

FOXP3 plays a crucial role in the development and function of regulatory T cells and was recently identified as a tumor suppressor in different cancer types.FOXP3 is expressed in normal brain tissues,but is strongly downregulated or absent in glioblastomas.In order to understand the FOXP3 adjustment mechanisms in glioma cell and provide a new method for glioma treatment.Firstly,a set of DNA microarray was done in U87 overexpressing FOXP3 to search the most significant genes and involved molecular biology way tested by Quantitative real-time PCR,Western blot analysis and immunohistochemistry in vitro and vivo.So we focus on ARHGAP15.We found FOXP3 can regulate the expression of ARHGAP15.Meanwhile,we collected 178 patients in clinical study.FOXP3 expression was correlated with ARHGAP15 in glioma samples.FOXP3 overexpression inhibited glioma cell migration via ARHGAP15 upregulation and Rac1 inactivation.Silencing FOXP3 promoted migration via ARHGAP15 downregulation and Rac1 activation.ARHGAP15,a GTPase activating protein for Rac1,inhibits small GTPase signaling in a dual negative manner.We found there is also a correlation between expression of ARHGAP15 and Glioma level.The small GTPase Rac1 plays an important role in cell migration.Thus,FOXP3 or ARHGAP15 may serve as a new molecular target for anti-metastatic therapies in treating glioma.Especially,the ARHGAP15 situated on the downstream of FOXP3 has more potential research value.