GRHL2 Suppresses Tumor Metastasis Via Regulation Of Transcriptional Activity Of RhoG In Non-small Cell Lung Cancer

Background and Aim:Lung cancer is one of the most common malignant tumors and poses a great threat to human health.Lung cancer could be divided into small cell lung cancer and non-small cell lung cancer,and non-small cell lung cancer accounts for about 80%-85% of lung cancer.Therefore,it is urgent to find new target of non-small cell lung cancer.The transcription factor,Grainyhead-like 2(GRHL2),is involved in wound healing,epidermal integrity,and epithelial-to-mesenchymal transition in various biological processes;however,the biological function of GRHL2 in non-small cell lung cancer is unknown.Methods:In the current study,we investigated the effect of GRHL2 on cell growth and migration in NSCLC cell lines and clinical tissues.Immunohistochemical analysis of clinical NSCLC specimens revealed that patients with high GRHL2 expression were associated with poor prognosis compared to patients with low GRHL2 expression.The cell transition was used to establish the lung cancer cell model with stable overexpressing or silencing of GRHL2,stably transfected cells were selected with puromycin and validated by western blotting.The metastasis capability of cell lines following overexpression or silencing of GRHL2 were detected by transwell and wound healing assays.Bioinformatic analysis predicted the target gene and signaling that may involved in its progression,and then verified the protein expression of targeted gene and pathway related genes using western blotting.GRHL2 decreasing the transcriptional activity of RhoG by directly binding to the RhoG promoter region was detected by luciferase.Conclusion: These findings provide evidence that GRHL2 is overexpressed in NSCLC cells and tissues.GRHL2 can decrease the transcriptional activity of RhoG by directly binding to the RhoG promoter region...