Novel KDM2B/SAV1 Signaling Pathway Promotes the Progression of Gastric Cancer.

Abstract

Salvador homologue 1 (SAV1), which is reported to act as a tumor suppressor in different types of cancer, is one of the key components of the Hippo pathway. However, the expression and mechanisms of SAV1 in the development and progression of gastric cancer (GC) remain to be elucidated. Immunohistochemistry (IHC) was performed in the present study to assess the expression levels of SAV1 and lysine-specific demethylase 2B (KDM2B) in GC tissues. The biological effects of SAV1 on GC cell proliferation, migration, and invasion were studied in vitro. KDM2B transcriptionally regulates SAV1 expression in several GC cell lines, and molecular experiments were performed to investigate underlying mechanisms. The expression level of SAV1 was significantly decreased in GC tissues and cell lines, negatively associated with tumor invasion depth, lymph node metastasis, and TNM stage, and positively associated with the overall survival of patients with GC. SAV1 overexpression inhibited the proliferation, migration, and invasion of GC cells. Further mechanistic studies revealed that KDM2B transcriptionally regulated SAV1 expression and further regulated the Hippo signaling pathway. To conclude, the present study demonstrated that KDM2B transcriptionally regulated SAV1 expression and promoted GC progression.