OncoTargets and Therapy (Aug 2019)
Transcription factor E2F1 positively regulates interferon regulatory factor 5 expression in non-small cell lung cancer
Abstract
Dan-dan Feng,1,* Qian Cao,1,* Dao-qi Zhang,2 Xiao-lu Wu,1 Cai-xia Yang,1 Yu-fei Chen,1 Tang Yu,3 Hai-xiao Qi,1 Guo-ping Zhou11Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China; 2Department of Pediatrics, Children’s Hospital of Soochow University, Soochow University, Suzhou, Jiangsu Province 215025, China; 3Department of Chest Surgery, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China*These authors contributed equally to this workCorrespondence: Guo-ping ZhouDepartment of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, 300 Guang Zhou Road, Nanjing, Jiangsu Province 210029, ChinaEmail [email protected]: Lung cancer is the most common malignant tumor in the world, and its incidence and mortality are very high. This study focuses on the mechanism of non-small cell lung cancer to find new therapeutic targets.Methods: We used RT-PCR and Western blot to verify the linear relationship between E2F1 and IRF5 in normal lung tissue and lung cancer tissues. Secondly, we used overexpression and knock down E2F1 in cell lines to detect the expression of IRF5. The prime enzyme reporter plasmid verified that E2F1 binds to the core promoter region of IRF5; finally, CHIP experiments demonstrated that E2F1 binds directly to IRF5.Results: We verified that E2F1 and IRF5 are decreased in patient tissues, and there is a strong linear relationship between E2F1 and IRF5. Secondly, we used overexpression of E2F1 or E2F1 siRNA transfected into HCC827 cells and found that E2F1 positively regulates the activity of the IRF5 promoter and the mRNA level of IRF5. Finally, the results of a chromatin immunoprecipitation assay demonstrated that E2F1 bound to the promoter region of IRF5 in vitro. These results suggested that the E2F1 transcription factor is the primary determinant for activating the basal transcription of the IRF5.Conclusion: The transcription factor E2F1 positively regulates IRF5 in non-small cell lung cancer.Keywords: interferon regulatory factor 5, E2F transcription factor 1, non-small cell lung cancer
