TRIP13 regulates progression of gastric cancer through mediating ubiquitination modification of DDX21

Abstract GC (Gastric cancer) is one of the most common malignant tumors, with over 95% of gastric cancer patients being adenocarcinoma and most gastric cancer patients having no obvious symptoms in the early stages. Therefore, finding biomarkers for early screening of gastric cancer and exploring new targets for gastric cancer treatment are urgent problems to be solved in the treatment of gastric cancer, it has important clinical significance in improving the survival rate of gastric cancer patients. The AAA + family ATPase thyroid hormone receptor interacting protein 13 (TRIP13) has been reported to play an important role in the development of various tumors, however, the biological function and mechanism of TRIP13 in gastric cancer are remain unclear. Here, our study confirms that TRIP13 is highly expressed in gastric cancer tissue samples, and that TRIP13 participates in the proliferation, migration, and invasion of gastric cancer cells. Mechanistically, our study confirms that TRIP13 directly interacts with DDX21 and stabilizes its expression by restraining its ubiquitination degradation, thereby promoting the progression of gastric cancer. Additionally, we found that histone deacetylase 1 (HDAC1) is an upstream factor of TRIP13, which could target the TRIP13 promoter region to promote the proliferation, migration, and invasion of gastric cancer cells. These results indicate that TRIP13 serve as a promising biomarker for the treatment of gastric cancer patients, and the HDAC1-TRIP13/DDX21 axis might provide solid theoretical basis for clinical treatment of gastric cancer patients.