Aim: Several Rho GTPase-activating proteins (Rho GAPs) have been proved to serve as tumor suppressors in diverse human cancers. Among them, ARHGAP25 has also been found to be associated with hematopoietic cells and regulate phagocytosis. Little is known about the role of ARHGAP25 in lung cancer cells.
Methods: Quantitative real-time PCR and Western blot were used to measure the expression levels of ARHGAP25. The ability of cell growth and mobility were measured by cell proliferation and Transwell assays. Chromatin immunoprecipitation and luciferase assay were conducted to identify the transcriptional regulation.
Results: Lung cancer tissues had much lower expression level of ARHGAP25 compared to non-cancerous specimens as well as for lung cancer cells. Cell growth and mobility were strongly reduced when ARHGAP25 was overexpressed. Further, significantly negative correlation between ARHGAP25 expression and Wnt signaling pathway was observed. Overexpression of ARHGAP25 reduced the expression of β-catenin and matrix metalloproteinase-7. ARHGAP25 knockdown effect of increased abilities of cell proliferation, migration and invasion could be reversed by adding XAV939 inhibitor. The promoter site of ARHGAP25 could be bound with HOXA4. HOXA4 could regulate the transcriptional activity of ARHGAP25.
Conclusions: This study suggests that ARHGAP25 may inhibit lung cancer cell growth, migration and invasion through Wnt/β-catenin signaling pathway and its transcriptional activity can be regulated by HOXA4.
Keywords: ARHAGP25, Wnt signaling pathway, HOXA4, lung cancer, biological function