ELK1 modulates SF3B3 transcriptional activity to stimulate proliferation and inhibit apoptosis in gastric cancer through the activation of the MAPK pathway.

Gastric cancer (GC) ranks as the fifth most common malignancy globally. Aberrant alternative splicing is implicated in tumorigenesis and progression. SF3B3, a key subunit of the spliceosome complex, is closely linked to alternative splicing dysfunction when its expression is dysregulated. This study delved into SF3B3's role and mechanisms in GC, aiming to uncover novel precision treatment targets. Through TCGA database analysis, SF3B3 was found to be upregulated in GC tissues, associated with poor prognosis and immune infiltration. In vitro experiments included cell culture, transduction, CCK-8, colony formation, scratch, migration, apoptosis assays, cell cycle analysis, and western blot, demonstrating that SF3B3 knockdown curbed GC cell proliferation, migration, and invasion, induced apoptosis and cell cycle arrest, while its overexpression had opposite effects. In vivo xenograft experiments showed that SF3B3 suppression markedly inhibits tumor growth. Transcriptome analysis and western blot suggested that SF3B3 promotes GC cell proliferation and impedes apoptosis by activating the MAPK pathway. Moreover, transcription factor ELK1 was shown to regulate SF3B3 expression, with a significant positive correlation between them. Overall, SF3B3 likely drives GC progression via the ELK1-SF3B3-MAPK axis, representing a potential precision treatment target for GC.