SMU1 knockdown suppresses gastric carcinoma growth, migration, and invasion and modulates the G0/G1 checkpoint of the cell cycle

Abstract

Abstract Gastric cancer (GC) is the third most common cause of cancer deaths globally, and its etiology remains unclear. Therefore, finding the key molecules that promote oncogenesis and progression of GC for treatment and diagnosis is necessary. SMU1, belonging to the WD40-repeat protein family, plays a significant role in DNA replication and RNA splicing. However, the function of SMU1 and the dysregulated mechanism of DNA replication in gastric cancer (GC) are still poorly understood. Here, we found that SMU1 was significantly upregulated in GC indicating a poor prognosis in GC patients by Kaplan–Meier method. Univariate and Multivariate Cox analyses showed that the high expression level of SMU1 was an independent risk factor for the prognosis of GC. Subsequently, the abilities of proliferation, invasion, and migration in SMU1 overexpression and downregulation cell were measured by CCK-8 assay, Transwells assay, and xenograft model experiment. In both in vivo and in vitro experiments, it was found that overexpression of SMU1 promoted GC cell proliferation, invasion, and migration, whereas SMU1 deficiency hampered GC aggressiveness. In addition, a flow cytometry assay revealed that the G0/G1 phase was arrested with SMU1 inhibition in GC cells. Based on these results, SMU1 plays a crucial role in carcinogenesis and GC progression, and it may also serve as a novel prognostic marker and potential therapeutic agent for GC.