KLF14 inhibits tumor progression via FOSL1 in glioma

Abstract

Abstract Background Glioma is the most common malignancy of the central nervous system. Fos-like antigen 1 (FOSL1) is overexpressed and acts as a tumor-promoting factor in glioma. However, the regulation of FOSL1 remains unknown. KLF14, a member of Kruppel-like factors that are involved gene transcription, plays an important role in the regulation of cell proliferation, differentiation and apoptosis. Loss of KLF14 triggers spontaneous tumorigenesis of lung, spleen and lymph node, suggesting its potential as biomarker for cancer. However, its role in glioma still needs to be deciphered. Therefore, we explore the interactions between FOSL1 and KLF14, as well as their role in glioma. Methods We first determined that FOSL1 can be transcriptional inhibited by KLF14 using dual-luciferase reporter gene assays and qPCR assays. Then, through immunohistochemistry (IHC)assay and western blotting (WB) assay in glioma tissues, we demonstrated a negative correlation between FOSL1 and KLF14. Next, KLF14 knockdown cells and double knockdown of KLF14 and FOSL1 cells were generated, and cell growth were detected by different experimental methods (MTT assay, crystal violet staining, cell migration assay). We then used qPCR and WB assay to search for and validate how KLF14 affects tumor cell migration through FOSL1. Finally, we confirmed the inhibition of tumor growth by KLF14 using xenograft tumor model. Results In this study, we showed that KLF14 inhibited the transcription of FOSL1.There is a negative correlation between KLF14 and FOSL1 in glioma tissues. Overexpression of KLF14 reversed the effect of FOSL1 in cell invasion, migration and epithelial-mesenchymal transition in glioma cells, and this was accompanied by the down-regulation of Snail2 and CD44. Moreover, KLF14 overexpression inhibits tumor progression in vivo. Conclusions The present results suggest that KLF14 is a new tumor molecular marker and a potential target for the treatment of glioma, providing a new target for anti-tumor drug research.