Ubiquitin specific peptidase 38 promotes the progression of gastric cancer through upregulation of fatty acid synthase.

Gastric cancer (GC) is a malignant tumor with an adverse health effect worldwide, whereas the underlying mechanism of GC development remains controversial. Identification of biomarkers is critical for the treatment of GC. Increasing evidence demonstrates that protein modification plays a pivotal role in carcinogenesis. USP38 is a member of the ubiquitin-specific protease (USP) family, which promotes protein stability by deubiquitinating the target proteins. In this study, we focused on the effect of USP38 on the GC and explored its underlying mechanism. The Cancer Genome Atlas (TCGA) database was used to evaluate the expression of USP38. AGS and HGC27 cells were treated with siRNA targeting USP38 or plasmids overexpressing USP38 to disturb levels of USP38. Immumohistochemical staining was performed to detect the level of USP38 and FASN. RT-qPCR and Western blotting (WB) were used to analyze the expression of mRNA and protein respectively. CCK8 assay, colony formation, cell migration assay, and cell apoptosis and cell cycle were performed to assess cell proliferation and migration ability. A subcutaneous tumor mice model was carried to verify the effect of USP38 on the GC in vivo. In this research, we found that USP38 was overexpressed in GC tissues, and USP38 contributed to GC cell proliferation, migration and tumorigenesis. Cell cycle and apoptosis were also regulated by USP38. Mechanistically, USP38 interacted with FASN, which resulted in enhanced protein stability of FASN and increased triglyceride production. Furthermore, FASN was critical for GC cell growth, migration and tumor development triggered by USP38 overexpression because its inhibitor orilistat reversed phenotypes in USP38 overexpressed GC cells. Collectively, USP38 overexpression is critical for GC cell growth, migration and tumorigenesis. Targeting FASN with inhibitors could be used as a potential treatment for GC patients with highly expressed USP38.