Promotion of Radioresistance of RACGAP1 in Digestive System Malignancy Through Impact on Cell Senescence
Abstract:
Background: RACGAP1 (Rac GTPase Activating Protein 1) belongs to RHOGAP, has been proved to be an oncogene in several tumors. Aims: In this study, we attempted to validate the promotion of radioresistance of RACGAP1 in digestive system malignancy and tried to uncover potential mechanism. Methods and results: Firstly, bioinformatics analyses for public datasets were taken. Then a series of in vitro experiments including CCK8 assay, Transwell migration and invasion experiments, and plate cloning formation experiment were conducted on digestive system malignancy. Finally, proteomics through iTRAQ (Isobaric tags for relative and absolute quantitation, iTRAQ) technology on colorectal cancer cell line LS411N with RACGAP1 knocked down was conducted and following bioinformatic analyses were carried out. In this study, we found that RACGAP1 is high expressed in digestive system malignancy and has negative effect on survival. RACGAP1 promotes proliferation, migration and invasion of pancreatic cancer in vitro. RACGAP1 promotes radioresistance in pancreatic cancer, esophageal squamous carcinoma and colorectal cancer in vitro. Proteomics of colorectal cancer cell line LS411N with RACGAP1 knocked down shows differentially expressed proteins got enriched in pathway of cell senescence.
Conclusion: RACGAP1 is a promising oncogene target for digestive system malignancy. RACGAP1 might promote radioresistance through its impact on cell senescence.
