Knockdown of TRIP13 inhibits gastric cancer stemness and cisplatin resistance by regulating FBXW7/ENO1 axis

Abstract

Purpose: To explore the role of thyroid hormone receptor interactor 13 (TRIP13) in gastric cancer (GC) and the associated mechanism. Methods: TRIP13 expression in GC was found in The Cancer Genome Atlas (TCGA) database and siTRIP13 was transfected in GC cells in order to generate cell lines with low TRIP13 expression. Cell proliferation was determined by colony formation assay, while cell migration  and invasion were evaluated by scratch test and Transwell assay, respectively. Sphere formation assay was used to assess cell stemness  characteristics whereas half-inhibitory concentration (IC50) value was evaluated by Cell Counting Kit-8 (CCK8). F-box and WD repeat  domain containing 7 (FBXW7) and enolase 1 (ENO1) expression were determined by western-blot assay. Results: TRIP13 was significantly expressed in GC based on TCGA database (p < 0.001) and high expression predicted poor prognosis in  GC patients (p < 0.05). Based on the findings of the cell function assay, si-TRIP13 inhibited the proliferation, migration, invasion and  stemness of GC cells (p < 0.001) and decreased the IC50 value. Mechanically, knockdown of TRIP13 decreased ENO1 expression level by  stabilizing FBXW7. Conclusion: TRIP13 functions as an oncogene in GC and stimulates growth and stemness via FBXW7/ENO1 pathway in  GC. Thus, a potential therapeutic target for the treatment of gastric cancer is provided by this study.