Splicing Factor 3b Subunit 4 (SF3B4) Promotes Proliferation of Gastric Cancer through Regulation of VDAC1

SF3B4 is a novel tumor related gene which is aberrantly expression in some malignant tumors. However, the role and mechanisms of SF3B4 in gastric cancer have not been explored. In this study, TMT-based quantitative proteomics and high content screening (HCS) revealed SF3B4 was strongly associated with GC. Immunohistochemistry revealed SF3B4 was upregulated in human gastric cancer tissues, and high SF3B4 expression was associated with shortened progression-free survival of patients. Further investigations indicated that the knockdown of SF3B4 could inhibit the proliferation and colony formation of GC cells while promoting cell apoptosis. Furthermore, knocking down SF3B4 could also inhibit the tumorigenicity of GC cells in vivo. RNA-sequencing followed by IPA was used to explore downstream of SF3B4 and identified VDAC1 as the potential target. Moreover, our study revealed that VDAC1 overexpression could alleviate the SF3B4 knockdown-induced inhibition of GC. Remarkably, we found for the first time that SF3B4 potentially facilitates the development of gastric cancer by exerting VDAC1-mediated effects on autophagy. SF3B4 promotes GC cell proliferation through regulate VDAC1 and may be a novel therapeutic target for GC.